(S)-(-)-Indoline-2-carboxylic acid

(S)-2, 3-dihydro-1 H-indole-2-carboxylic acid: Conversion of (S)-2-bromophenylalanine with 2 molpercent CuCl in NMP at 100°C A flask was charged successively with 366 mg (1.5 mmol) (S)-2-bromophenylalanine, 217 mg (1.6 mmol) KA flask was charged successively with 366 mg (1.5 mmol) (S)-2-bromophenylalanine, 217 mg (1.6 mmmol) KExample 3 (S)-2, 3-dihydro-1 H-indole-2-carboxylic acid: Conversion of (S)-2-bromophenylalanine with 2 molpercent CuCl in water at 95°C A flask was charged successively with 366 mg (1.5 mmol) (S)-2-bromophenylalanine, 217 mg (1.6 mmol) K(S)-2, 3-dihydro-1 H-indole-2-carboxylic acid: Conversion of (S)-2- bromophenylalanine with 0.01 molpercent CuCI in water at 95°C EPO (S)-2, 3-dihydro-1H-indole-2-carboxylic acid: Conversion of (S)-2- bromophenylalanine with 1 molpercent CuCI in NMP at 80Examplei; (S)-2, 3-dihydro-1H-indole-2-carboxylic acid: Conversion of (S)-2-bromophenylalanine with 2 molpercent CuCI in NMP at 100(S)-2, 3-dihydro-1 H-indole-2-carboxylic acid: Conversion of (S)-2- bromophenylalanine with 2 molpercent CuCI in water at 95°C; A flask was charged successively with 366 mg (1.5 mmol) (S)-2- bromophenylalanine, 217 mg (1.6 mmol) K(S)-2, 3-dihydro-1H-indole-2-carboxylic acid: Conversion of (S)-2- bromophenylalanine without CuCI in water at 95°C; A flask was charged successively with 366 mg (1.5 mmol) (S)-2- bromophenylalanine, 217 mg (1.6 mmmol) KIn a 1000 ml autoclave, 78 g of indole-2-carboxylic acid and 200 ml of ethanol were added. After adding 8 g of phosphorus iodide and a concentrated hydroiodic acid catalyst, the mixture was filled with carbon dioxide to a pressure of 5 kg. After re-evacuating three times, Pressure to 10 kg, and then re-exhaust gas three times, after the exhaust gas flushing carbon disulfide pressure to 20 kg, and then hydrogen pressure 35 kg, temperature 90 ° C hydrogenation, until the hydrogen pressure is not reduced, the reaction time of about 5 hours, the reaction was completed Cooling exhaust, discharging, suction filtration catalyst recovery, and then recovered ethanol after distillation colorless liquid 56 grams, a yield of 87.5percent, a purity of 93.5percent.A flask was charged successively with 3.00 g (15.0 mmol) (S)-2-amino-3-(2-chloro-phenyl)-propionic acid, 2.17 g (15.7 mmol) KStep (iii):; (S)-2, 3-dihvdro-1 H-indole-2-carboxylic acid: Conversion of (S)-2-amino-3-(2- chloro-phenyD-propionic acid with 1 molpercent CuCI in water at 95°C; A flask was charged successively with 3.00 g (15.0 mmol) (S)-2- amino-3-(2-chloro-phenyl)-propionic acid, 2.17 g (15.7 mmol) KExample 3 [70] Preparation of (S) -indoline-2-Carboxylic Acid Through Hydrolysis; [71] Into a 250 ml reactor equipped with a pH meter, 8.1 g of (S)-indoline-2-carboxylic acid methyl ester prepared in and 50 ml of 1N aqueous sodium hydroxide solution were placed and strongly stirred at room temperature. Whether (S) -indoline-2-carboxylic acid methyl ester was converted to (S)-indoline-2-carboxylic acid was confirmed. Then, while the temperature of the reactor was maintained at 20 C or less, 1N aqueous hydrochloric acid solution was slowly added to the reactor to control pH 5. The resultant reaction product was extracted three times with 50 ml of ethyl acetate by use of the separating funnel, and the organic layer was placed into a round bottom flask. The solvent in the organic layer was removed through distillation The product obtained in step 4-2 (0.25 mol, 54.8 g) was added to a 500 mL three-necked flask, And the newly prepared 30percent sulfuric acid aqueous solution 300mL, Heated to reflux.Solid gradually dissolved, TLC (developing solvent: chloroform: methanol: triethylamine = 6: 4: 1)Tracking to the raw point of the reaction is complete, stop heating, Naturally cool to room temperature.Then adjust the pH to 4 to 5 with 10percent aqueous sodium hydroxide solution, A large amount of white solid precipitated. Filter, The filter cake was washed three times with 50 mL of water, dried in vacuo, A white solid was obtained 35.4 g, The yield was 86.8percentPurity 97.1percent (HPLC), Step A