CN110194760B - Process for preparing 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindol-1-ones - Google Patents
Process for preparing 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindol-1-ones Download PDFInfo
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Abstract
The invention discloses a method for preparing 3-benzylidene-2- (7' -quinoline) -2, 3-dihydroA method for preparing (E) -isoindole-1-ketone compounds, which comprises the following steps: the benzoic acid compound, the styrene compound and the 7-aminoquinoline fully react in an organic solvent reaction medium under the promotion of organic base by taking transition metal as a catalyst to prepare a product, the product is subjected to post-treatment to prepare the 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-ketone compound,
formula (I) R1Selected from one of the following: hydrogen, methyl, methoxy; r2Selected from one of the following: alkyl, aryl, ether, ester groups; the preparation condition is mild, and the reaction is carried out under the normal pressure condition; the cost is saved, and the requirement on equipment is low; the boiling point of the used solvent is low, so that energy is saved; the post-treatment is convenient, the environment-friendly requirement is met, and the obtained product has great industrial application prospect in the fields of chemical industry and material synthesis.
Description
Technical Field
The invention belongs to the technical field of preparation of pharmaceutical synthesis intermediates, and particularly relates to a method for preparing 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-ketone compounds by palladium catalysis.
Background
The 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-ketone compound is an important medical synthetic intermediate and has wide and important application in the fields of synthetic industry and medical industry. The 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-ketone compound exists in a plurality of natural organic matters and core structures of physiological active substances, is used for treating diseases of gastric cancer, esophagus cancer and pancreas cancer, and has wide medical and biochemical application prospects. Meanwhile, the 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-ketone compound can also be used as a chiral auxiliary agent for asymmetric synthesis, can be used as a chiral ligand after reduction, and has potential application prospect in asymmetric synthesis. Because of good physiological activity and reactivity and the like. The synthesis research thereof has been a research hotspot in recent years. The reported preparation method of the 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-ketone compound is obtained by coupling reaction and cyclization through transition metal catalysis, Stille reaction, Suzuki reaction and the like. However, the above methods have disadvantages of many reaction steps, low reaction efficiency, and the like. The method uses palladium as a catalyst, realizes the high-efficiency preparation of the 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-ketone compound by one step, and has the advantages of low cost, simple and easily obtained raw materials, wide application range, excellent yield, convenient product treatment and environmental protection. Has important application prospect in the field of related pharmaceutical intermediate synthesis industry.
Disclosure of Invention
Aiming at the problems in the prior art, the invention aims to provide a method for preparing 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-ketone compounds by palladium catalysis.
The invention is realized by the following technical scheme:
the method for preparing the 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-ketone compound shown in the formula (IV) by palladium catalysis is characterized by comprising the following steps: fully reacting a benzoic acid compound shown as a formula (I), a styrene compound shown as a formula (II) and 7-aminoquinoline shown as a formula (III) in an organic solvent reaction medium under the promotion of organic base by using transition metal as a catalyst to prepare a product, and carrying out post-treatment on the product to prepare a 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-one compound; the transition metal catalyst was 10mmol% tetrakis triphenylphosphine palladium (Pd (PPh)3)4) The organic base is triethylamine, and the organic solvent is 1,4-Dioxane (1, 4-Dioxane);
formula (I) R1Selected from one of the following: hydrogen, methyl, methoxy; r2Selected from one of the following: alkyl, aryl, ether, ester.
The method for preparing the 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-ketone compound by palladium catalysis is characterized in that the ratio of the benzoic acid compound to the styrene compound to the solvent 1,4-dioxane is 5mmol/5mmol/15 mL.
The method for preparing the 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-ketone compound by palladium catalysis is characterized in that the ratio of the benzoic acid compound to the styrene compound to the triethylamine is 5mmol/5mmol/10 mmol.
The method for preparing the 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-ketone compound by palladium catalysis is characterized in that the ratio of the benzoic acid compound to the styrene compound to the palladium tetratriphenylphosphine is 5mmol/5mmol/0.5 mmL.
The method for preparing the 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-ketone compound by palladium catalysis is characterized in that the equivalent ratio of the benzoic acid compound to the styrene compound to the 7-aminoquinoline is 1:1:1.2-1:1: 1.5.
The method for preparing the 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-ketone compound by palladium catalysis is characterized in that the reaction temperature is 100 ℃, the reaction time is 8 hours, and the reaction is under the protection of nitrogen.
The method for preparing the 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-ketone compound by palladium catalysis is characterized by comprising the following steps:
1) and (3) extraction: after the reactant is cooled to room temperature at normal temperature, 10mL of saturated sodium chloride aqueous solution is added into the reactant, then ethyl acetate is used for extraction for 3 times, 10mL of the saturated sodium chloride aqueous solution is used for each time, and the extraction liquid is combined;
2) concentration: drying the extract with anhydrous sodium sulfate, and rotary drying with rotary evaporator to obtain concentrate;
3) adsorbing the concentrate with column chromatography silica gel, adding into 200-300 mesh chromatography silica gel column, and purifying with n-hexane: performing flash column chromatography with ethyl acetate according to a certain proportion, mixing eluates, spin-drying with a rotary evaporator, and pumping with an oil pump to obtain the product 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-one compound.
The method for preparing the 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-ketone compound by palladium catalysis is characterized in that the drying time in the step 2) is 1 hour.
The method for preparing the 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-ketone compound by palladium catalysis is characterized in that the ratio of n-hexane to ethyl acetate in the step 3) is 5:1-3: 1.
The preparation condition is mild, and the reaction is carried out under the normal pressure condition; the cost is saved, and the requirement on equipment is low; the boiling point of the used solvent is low, so that energy is saved; the post-treatment is convenient, the environment-friendly requirement is met, and the obtained product has great industrial application prospect in the fields of chemical industry and material synthesis.
Detailed Description
The present invention will be described in more detail with reference to specific examples.
In the synthesis step of the invention, 5mmol of benzoic acid compound 1, 6mmol of styrene compound 2 and 5mmol of 7-aminoquinoline 3 are respectively added into a 25mL round-bottom flask, then 15mL1, 4-dioxane and 10mmol of triethylamine are sequentially added, and the reaction is stirred for 8 hours at 100 ℃. After the reaction is completed, 15mL of saturated sodium chloride aqueous solution is added into the system, ethyl acetate is used for extraction for 3 times, 10mL of the saturated sodium chloride aqueous solution is used for each time, organic phases are combined, after anhydrous sodium sulfate is used for drying, the solvent is evaporated, and 200-mesh and 300-mesh silica gel column chromatography is carried out to obtain 4 pure products of the 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-one compounds, wherein the yield is 81-96%. Specific examples and characterization data all product structures were determined by comparison of nuclear magnetic resonance and mass spectrometry results as follows.
Example 1: preparation of product 4a
610mg (5mmol) of benzoic acid 1a, 625mg (6mmol) of styrene 2a and 721mg (5mmol) of 7-aminoquinoline 3a are each introduced into a 25mL round-bottomed flask at room temperature, followed by 578mg (0.5mmol) of tetratriphenylphosphine palladium, 15mL of 1,4-dioxane and 1010mg (10mmol) of triethylamine in that order and stirred at 100 ℃ for 8 hours. After the reaction, 15mL of saturated aqueous sodium chloride solution was added to the system, extraction was performed 3 times with ethyl acetate, 10mL each time, the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was evaporated, and 200-mesh 300-mesh silica gel column chromatography was performed to obtain pure 4a (1411mg, yield 81%, pale yellow solid).
1H NMR(400MHz,CDCl3)δ8.86(dd,J＝4.2,1.7Hz,1H),7.98(dd,J＝11.2,4.6Hz,2H),7.89(d,J＝7.8Hz,1H),7.69(td,J＝7.6,1.1Hz, 1H),7.60–7.54(m,2H),7.48(dd,J＝7.3,1.4Hz,1H),7.33–7.27(m, 2H),6.81(s,1H),6.67(dd,J＝11.1,4.3Hz,1H),6.58–6.51(m,4H). 13C NMR(101MHz,CDCl3)δ168.25,150.47,144.47,138.77,136.16, 135.92,134.26,133.62,132.36,130.14,129.19,128.94,128.49,128.38, 128.22,126.39,126.12,125.75,124.03,121.33,119.76,107.49,77.50, 77.18,76.86.
Example 2: preparation of product 4b
783mg (5mmol) of p-chlorobenzoic acid 1b, 625mg (6mmol) of styrene 2a and 721mg (5mmol) of 7-aminoquinoline 3a were each charged in a 25mL round-bottomed flask at room temperature, followed by 578mg (0.5mmol) of tetratriphenylphosphine palladium, 15mL1, 4-dioxane and 1010mg (10mmol) of triethylamine in that order, and stirred at 100 ℃ for 8 hours. After the reaction is completed, 15mL of saturated aqueous sodium chloride solution is added into the system, extraction is carried out for 3 times by ethyl acetate, 10mL of saturated aqueous sodium chloride solution is used for each time, organic phases are combined, after drying by anhydrous sodium sulfate, the solvent is evaporated, and silica gel column chromatography with 300 meshes is carried out to obtain a pure product 4b (1589mg, yield 83 percent, light yellow solid).
1H NMR(400MHz,CDCl3)δ8.84(dd,J＝4.2,1.7Hz,1H),7.97(dd,J＝8.3,1.7Hz,1H),7.92(d,J＝8.1Hz,1H),7.87(d,J＝1.6Hz,1H),7.59 (dd,J＝8.2,1.4Hz,1H),7.53(dd,J＝8.1,1.7Hz,1H),7.48(dd,J＝7.4, 1.4Hz,1H),7.32–7.28(m,2H),6.78(s,1H),6.69(dt,J＝8.8,4.3Hz, 1H),6.54(d,J＝4.5Hz,4H).
13C NMR(101MHz,CDCl3)δ167.27,150.53,144.35,140.32,138.84, 135.95,135.19,134.00,133.19,130.12,129.60,128.98,128.66,128.21, 126.79,126.48,126.41,125.78,125.37,121.43,120.18,108.69,77.48, 77.16,76.84.
Example 3: preparation of product 4c
681mg (5mmol) of p-methylbenzoic acid 1c, 625mg (6mmol) of styrene 2a and 721mg (5mmol) of 7-aminoquinoline 3a are each added to a 25mL round-bottomed flask at room temperature, followed by 578mg (0.5mmol) of tetratriphenylphosphine palladium, 15mL1, 4-dioxane and 1010mg (10mmol) of triethylamine in that order, and stirring is carried out at 100 ℃ for 8 hours. After the reaction is completed, 15mL of saturated aqueous sodium chloride solution is added into the system, extraction is carried out for 3 times by ethyl acetate, 10mL of saturated aqueous sodium chloride solution is used for each time, organic phases are combined, after drying by anhydrous sodium sulfate, the solvent is evaporated, and silica gel column chromatography with 300 meshes is carried out to obtain a 4c pure product (1667mg, the yield is 92%, and a light yellow solid is obtained).
1H NMR(400MHz,CDCl3)δ8.84(dd,J＝4.2,1.6Hz,1H),7.96(dd,J＝8.3,1.6Hz,1H),7.87(d,J＝7.8Hz,1H),7.68(s,1H),7.57(d,J＝8.2 Hz,1H),7.47(dd,J＝7.3,1.2Hz,1H),7.37(d,J＝7.2Hz,1H),7.31– 7.27(m,2H),6.77(s,1H),6.67(t,J＝6.4Hz,1H),6.56–6.49(m,4H), 2.55(s,3H).
13C NMR(101MHz,CDCl3)δ168.33,150.41,144.47,143.04,139.14, 136.24,135.90,134.36,133.73,130.32,130.13,129.60,128.92,128.37, 128.21,126.35,126.01,125.74,123.87,121.27,120.07,107.04,77.46, 77.14,76.83,22.30.
Example 4: preparation of product 4d
761mg (5mmol) of p-methoxybenzoic acid 1d, 625mg (6mmol) of styrene 2a and 721mg (5mmol) of 7-aminoquinoline 3a are each introduced into a 25mL round-bottomed flask at room temperature, followed by 578mg (0.5mmol) of tetratriphenylphosphine palladium, 15mL1, 4-dioxane and 1010mg (10mmol) of triethylamine in that order, and the mixture is stirred at 100 ℃ for 8 hours. After the reaction is completed, 15mL of saturated aqueous sodium chloride solution is added into the system, extraction is carried out for 3 times by ethyl acetate, 10mL of saturated aqueous sodium chloride solution is used for each time, organic phases are combined, after drying by anhydrous sodium sulfate, the solvent is evaporated, and silica gel column chromatography with 300 meshes is carried out to obtain 4d pure product (1608mg, yield 85%, light yellow solid).
1H NMR(400MHz,CDCl3)δ8.84(dd,J＝4.2,1.7Hz,1H),7.96(dd,J＝8.3,1.7Hz,1H),7.89(d,J＝8.4Hz,1H),7.56(dd,J＝8.2,1.3Hz,1H), 7.47(dd,J＝7.4,1.4Hz,1H),7.33(d,J＝2.1Hz,1H),7.30–7.26(m, 2H),7.09(dd,J＝8.4,2.2Hz,1H),6.74(s,1H),6.67(ddd,J＝8.7,4.7, 1.9Hz,1H),6.57–6.50(m,4H),3.96(s,3H).
13C NMR(101MHz,CDCl3)δ168.05,163.62,150.40,144.52,141.05, 136.20,135.91,134.41,133.63,130.16,128.95,128.34,128.23,126.38, 126.09,125.76,125.56,121.38,121.27,116.58,107.12,103.81,77.48, 77.16,76.84,55.94.
Example 5: preparation of product 4e
991mg (5mmol) of p-phenylbenzoic acid 1d, 625mg (6mmol) of styrene 2a and 721mg (5mmol) of 7-aminoquinoline 3a are each introduced into a 25mL round-bottomed flask at room temperature, followed by 578mg (0.5mmol) of tetratriphenylphosphine palladium, 15mL of 1,4-dioxane and 1010mg (10mmol) of triethylamine in that order, and the mixture is stirred at 100 ℃ for 8 hours. After the reaction, 15mL of saturated aqueous sodium chloride solution was added to the system, extraction was performed 3 times with 10mL of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was evaporated, and silica gel column chromatography was performed with 300 mesh to obtain pure 4e (1825mg, yield 86%, pale yellow solid).
1H NMR(400MHz,CDCl3)δ8.86(dd,J＝4.2,1.7Hz,1H),8.07–8.04 (m,2H),7.97(dd,J＝8.3,1.7Hz,1H),7.78(dd,J＝7.9,1.4Hz,1H), 7.72(dd,J＝8.1,1.0Hz,2H),7.59(dd,J＝8.2,1.3Hz,1H),7.54–7.50 (m,3H),7.45(d,J＝7.2Hz,1H),7.33–7.29(m,2H),6.88(s,1H),6.71 –6.65(m,1H),6.58–6.51(m,4H).
13C NMR(101MHz,CDCl3)δ168.10,150.49,145.82,144.48,140.81, 139.42,136.25,135.95,135.12,134.33,133.64,130.23,129.14,129.00, 128.58,128.51,128.27,127.69,127.28,126.43,126.16,125.81,124.47, 121.36,118.54,107.58,77.48,77.16,76.84.
Example 6: preparation of product 4f
610mg (5mmol) of benzoic acid 1a, 832mg (6mmol) of p-chlorostyrene 2b and 721mg (5mmol) of 7-aminoquinoline 3a are each added in a 25mL round-bottomed flask at room temperature, followed by 578mg (0.5mmol) of tetratriphenylphosphine palladium, 15mL1, 4-dioxane and 1010mg (10mmol) of triethylamine in that order and stirred at 100 ℃ for 8 hours. After the reaction, 15mL of saturated aqueous sodium chloride solution was added to the system, extraction was performed 3 times with 10mL of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was evaporated, and silica gel column chromatography was performed with 300 mesh to obtain pure 4f (1608mg, yield 84%, pale yellow solid).
1H NMR(400MHz,CDCl3)δ8.83(dd,J＝4.2,1.7Hz,1H),8.04–7.97 (m,2H),7.87(d,J＝7.8Hz,1H),7.69(dd,J＝13.6,7.3Hz,2H),7.58(t, J＝7.5Hz,1H),7.51(d,J＝7.3Hz,1H),7.38–7.30(m,2H),6.71(s, 1H),6.50–6.43(m,4H).
13C NMR(101MHz,CDCl3)δ168.13,150.54,144.38,138.52,136.86, 136.01,134.17,132.49,132.09,131.91,130.25,129.43,129.38,129.00, 128.62,128.39,126.36,125.89,124.14,121.54,119.81,105.91,77.48, 77.16,76.84.
Example 7: preparation of 4g of product
610mg (5mmol) of benzoic acid 1a, 805mg (6mmol) of o-methoxystyrene 2c and 721mg (5mmol) of 7-aminoquinoline 3a are each introduced at room temperature in a 25mL round-bottomed flask, followed in turn by 578mg (0.5mmol)) Tetratriphenylphosphine palladium, 15mL1, 4-dioxane and 1010mg (10mmol) triethylamine were stirred at 100 ℃ for 8 h. After the reaction was completed, 15mL of a saturated aqueous solution of sodium chloride was added to the system, and the mixture was extracted with ethyl acetate for 3 times (10 mL each time), the organic phases were combined, dried over anhydrous sodium sulfate, the solvent was distilled off, and the mixture was subjected to 200-mesh 300-mesh silica gel column chromatography to obtain 4g of a pure product (179. mg, yield 95%, colorless solid).1H NMR(400MHz,CDCl3)δ8.86(dd,J＝4.2,1.7Hz,1H),7.99–7.98 (m,1H),7.97–7.95(m,1H),7.92(d,J＝7.8Hz,1H),7.67(td,J＝7.6, 1.1Hz,1H),7.55(td,J＝7.9,4.1Hz,2H),7.48(dd,J＝7.3,1.4Hz,1H), 7.31–7.27(m,2H),6.76(s,1H),6.67(ddd,J＝8.5,7.6,1.2Hz,1H), 6.30(t,J＝8.2Hz,2H),5.92(td,J＝7.4,0.7Hz,1H),3.58(s,3H).
13C NMR(101MHz,CDCl3)δ168.33,156.18,150.34,144.60,138.77, 136.38,135.95,134.10,132.22,130.05,130.00,129.00,128.79,128.46, 128.39,127.93,125.52,123.91,122.52,121.11,120.10,118.57,108.84, 103.92,77.48,77.16,76.84,55.03.
Example 8: preparation of product 4h
610mg (5mmol) of benzoic acid 1a, 877mg (6mmol) of p-propylstyrene 2d and 721mg (5mmol) of 7-aminoquinoline 3a are each introduced into a 25mL round-bottomed flask at room temperature, followed by 578mg (0.5mmol) of tetratriphenylphosphine palladium, 15mL of 1,4-dioxane and 1010mg (10mmol) of triethylamine in that order, and the mixture is stirred at 100 ℃ for 8 hours. After the reaction is completed, 15mL of saturated sodium chloride aqueous solution is added into the system, ethyl acetate is used for extraction for 3 times, 10mL of the saturated sodium chloride aqueous solution is used for each time, organic phases are combined, after anhydrous sodium sulfate is used for drying, the solvent is evaporated, and silica gel column chromatography with 300 meshes is carried out to obtain a pure product (1757mg, the yield is 90 percent, and light yellow solid) for 4 hours.
1H NMR(400MHz,CDCl3)δ8.83(dd,J＝4.2,1.7Hz,1H),8.00–7.92 (m,2H),7.86(d,J＝7.8Hz,1H),7.66(td,J＝7.6,1.1Hz,1H),7.54(dd, J＝7.8,6.9Hz,2H),7.47(dd,J＝7.4,1.3Hz,1H),7.30–7.26(m,2H), 6.79(s,1H),6.45(d,J＝7.9Hz,2H),6.32(d,J＝8.0Hz,2H),2.22(t,J＝7.5Hz,2H),1.42–1.32(m,2H),0.80(t,J＝7.3Hz,3H).
13C NMR(101MHz,CDCl3)δ168.18,150.40,144.54,140.56,138.80, 135.89,135.81,134.38,132.26,130.89,130.11,129.02,128.88,128.32, 128.08,126.53,125.72,123.98,121.25,119.70,107.73,77.48,77.16, 76.84,37.53,24.47,13.80。
Claims (9)
1. A process for producing a 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindol-1-one compound represented by the following formula (IV), which comprises the steps of: fully reacting a benzoic acid compound shown as a formula (I), a styrene compound shown as a formula (II) and 7-aminoquinoline shown as a formula (III) in an organic solvent reaction medium under the promotion of organic base by using transition metal as a catalyst to prepare a product, and carrying out post-treatment on the product to prepare a 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-one compound; the transition metal catalyst was 10mmol% tetrakis triphenylphosphine palladium (Pd (PPh)3)4) The organic base is triethylamine, and the organic solvent is 1,4-Dioxane (1, 4-Dioxane);
in the reaction formula, R1Selected from one of the following: hydrogen, methyl, methoxy; r2Selected from one of the following: hydrocarbon groups, ether groups, ester groups.
2. The process for the preparation of 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindol-1-one compounds according to claim 1, characterized in that the ratio of benzoic acid compound, styrene compound and solvent 1,4-dioxane is 5mmol/5mmol/15 mL.
3. The process for the preparation of 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindol-1-one compounds according to claim 1, characterized in that the ratio of benzoic acid compound, styrene compound and triethylamine is 5mmol/5mmol/10 mmol.
4. The process for the preparation of 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindol-1-one compounds according to claim 1, characterized in that the ratio of benzoic acid, styrene compound and palladium tetratriphenylphosphine is 5mmol/5mmol/0.5 mmol.
5. The process for the preparation of 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindol-1-one compounds according to claim 1, characterized in that the equivalent ratio of benzoic, styrenic and 7-aminoquinoline is 1:1:1.2-1:1: 1.5.
6. The process for preparing 3-benzylidene-2- (7' -quinolino) -2, 3-dihydro-isoindol-1-ones according to claim 1, wherein the reaction temperature is 100 ℃ and the reaction time is 8 hours, under nitrogen.
7. The process for the preparation of 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindol-1-one compounds according to claim 1, characterized in that the specific process of work-up consists of the following steps:
1) and (3) extraction: after the reactant is cooled to room temperature at normal temperature, 10mL of saturated sodium chloride aqueous solution is added into the reactant, then ethyl acetate is used for extraction for 3 times, 10mL of the saturated sodium chloride aqueous solution is used for each time, and the extraction liquid is combined;
2) concentration: drying the extract with anhydrous sodium sulfate, and rotary drying with rotary evaporator to obtain concentrate;
3) adsorbing the concentrate with column chromatography silica gel, adding into 200-300 mesh chromatography silica gel column, and purifying with n-hexane: performing flash column chromatography with ethyl acetate according to a certain proportion, mixing eluates, spin-drying with a rotary evaporator, and pumping with an oil pump to obtain the product 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindole-1-one compound.
8. The process for preparing 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindol-1-one compounds according to claim 7, wherein the drying time in step 2) is 1 hour.
9. The process for preparing 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindol-1-one compounds according to claim 7, wherein the ratio of n-hexane to ethyl acetate in step 3) is 5:1 to 3: 1.
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| WO2014025978A1 (en) * | 2012-08-09 | 2014-02-13 | Celgene Corporation | Processes for the preparation of (s)-3-4-((4-(morpholinomethyl) benzyl)oxy)-1-oxoisoindolin-2-yl) piperidine-2,6-dione and pharmaceutically acceptable forms thereof |
| CN104130187A (en) * | 2014-05-27 | 2014-11-05 | 浙江工业大学 | asymmetric synthesis method of chiral dihydroquinolinone compound |
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