(2S)-3-methyl-2-phenylbutan-1-amine

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To (±)-2-(3-benzoylphenyl)propionic acid (1200 g, 4.719 mol) were added methyl-t-butyl ether (hereinafter abbreviated to "MTBE") (4.8 L) and water (600 g, water/KET=0.50) and the mixture was dissolved with heating. Then, (S)-(+)-3-methyl-2-phenylbutylamine (388 g, 2.377 mol) was added dropwise with stirring at 50° C. to 55° C. This reaction solution was cooled to precipitate a crystal and then reheated from 35° C. to 50° C. This solution was again cooled and then reheated from 40° C. to 45° C. This solution was cooled slowly to 10° C. and stirred at 5° C. to 10° C. for one hour. Then, the crystal precipitated was filtered, and the filter cake was washed three times with cold MTBE (1 L) and dried. In this manner, a diastereomer salt (741 g, 1.775 mol) of (S)-(+)-2-(3-benzoylphenyl)propionic acid with (S)-(+)-3-methyl-2-phenylbutylamine was obtained. The yield of the product based on (S)-(+)-2-(3-benzoylphenyl)propionic acid contained in the starting material was 75.2% and the optical purity was 99.1% e.e. the mixture was dissolved with heating This reaction solution was cooled to precipitate a crystal reheated from 35° C. to 50° C This solution was again cooled reheated from 40° C. to 45° C stirred at 5° C. to 10° C. for one hour Then, the crystal precipitated was filtered the filter cake was washed three times with cold MTBE (1 L) dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (±)-2-(3-Benzoylphenyl)propionic acid (51 g, 0.2 mol) was dissolved in MIBK (290 ml) and (S)-(+)-3-methyl-2-phenylbutylamine (19.6 g, 0.12 mol) was added dropwise with stirring. After completing the addition, the reaction solution was maintained at 35° C. to 40° C. for one hour and stirred at room temperature for 5 hours and then at 10° C. for 3 hours. Then, the crystal precipitated was filtered and the filter cake was washed with cold MIBK (70 ml) to give a wet cake (67 g). To this wet cake was added MIBK (240 ml) and the mixture was heated to dissolve at 77° C. Then, the mixture was cooled and stirred at 10° C. for 2 hours. Then, the crystal precipitated was filtered to give a diastereomer salt (30.2 g) of (S)-(+)-2-(3-benzoylphenyl)propionic acid with (S)-(+)-3-methyl-2-phenylbutylamine. This diastereomer salt was treated with hydrochloric acid to give (S)-(+)-2-(3-benzoylphenyl)propionic acid (18.26 g). The optical purity of this propionic acid was 99.2% e.e. The yield of the product based on (S)-(+)-2-(3-benzoylphenyl)propionic acid contained in the starting material was 71.6% e.e. the addition the reaction solution was maintained at 35° C. to 40° C. for one hour stirred at room temperature for 5 hours Then, the crystal precipitated was filtered the filter cake was washed with cold MIBK (70 ml) to give a wet cake (67 g) the mixture was heated to dissolve at 77° C Then, the mixture was cooled stirred at 10° C. for 2 hours Then, the crystal precipitated was filtered

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: That is, (±)-2-(3-benzoylphenyl)propionic acid (12.7 g, 50 mmol) was dissolved in MIBK (76 ml) and (S)-(+)-3-methyl-2-phenylbutylamine (4.9 g, 30 mmol) was added dropwise at 40° C. This reaction solution was stirred at 35° C. to 40° C. for one hour, followed by at room temperature for 5 hours and then at 10° C. to 15° C. for one hour. Then, the crystal precipitated was filtered, and the filter cake was washed with cold MIBK (30 ml) and dried to give a diastereomer salt (8.34 g) of (S)-(+)-2-(3-benzoylphenyl)propionic acid with (S)-(+)-3-methyl-2-phenylbutylamine. The yield of the product based on (S)-(+)-2-(3-benzoylphenyl)propionic acid contained in the starting material was 80%. Melting point: 129°-131° C. Optical purity: 94.3% e.e. followed by at room temperature for 5 hours at 10° C. to 15° C. for one hour Then, the crystal precipitated was filtered the filter cake was washed with cold MIBK (30 ml) dried

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (±)-2-(3-Benzoylphenyl)propionic acid (12.7 g, 50 mmol) was added to tetrahydrofuran (hereinafter abbreviated to "THF") (45 ml) and dissolved. Then, (S)-(+)-3-methyl-2-phenylbutylamine (4.1 g, 25 mmol) was added dropwise with stirring. After completing the addition, the reaction solution was maintained at 35° C. to 40° C. for one hour, stirred at room temperature for 4 hours, and then cooled to 10° C. The crystal precipitated was filtered, and the filter cake was washed with cold THF (35 ml) and then dried to give a diastereomer salt (5.84 g) of (S)-(+)-2-(3-benzoylphenyl)propionic acid with (S)-(+)-3-methyl-2-phenylbutylamine. The yield of the product based on (S)-(+)-2-(3-benzoylphenyl)propionic acid contained in the starting material was 56% and the optical purity was 94.3% e.e. dissolved the addition the reaction solution was maintained at 35° C. to 40° C. for one hour stirred at room temperature for 4 hours The crystal precipitated was filtered the filter cake was washed with cold THF (35 ml) dried

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (±)-2-(3-Benzoylphenyl)propionic acid (12.7 g, 50 mmol) was added to methyl ethyl ketone (hereinafter abbreviated to "MEK") (70 ml) and dissolved with heating. Then, (S)-(+)-3-methyl-2-phenylbutylamine (4.9 g, 30 mmol) was added dropwise with stirring. After completing the addition, the reaction solution was stirred at 35°C. to 40°C. for one hour and then at room temperature for 4 hours, and finally maintained at 10°C. for 3 hours. The crystal precipitated was filtered, and the filter cake was washed with cold MEK (35 ml) and dried to give a diastereomer salt (7.72 g) of (S)-(+)-2-(3-benzoylphenyl) propionic acid with (S)-(+)-3-methyl-2-phenylbutylamine. The yield of the product based on (S)-(+)-2-(3-benzoylphenyl) propionic acid contained in the starting material was 74%. dissolved with heating the addition the reaction solution was stirred at 35°C. to 40°C. for one hour The crystal precipitated was filtered the filter cake was washed with cold MEK (35 ml) dried

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (±)-2-(3-Benzoylphenyl)propionic acid (12.7 g, 50 mmol) was added to MIBK (70 ml) and dissolved with heating to 35° C. Then, (S)-(+)-3-methyl-2-phenylbutylamine (5.24 g, 32 mmol) was added dropwise with stirring. After completing the addition, the reaction solution was stirred at 35° C. to 40° C. for one hour, followed by at room temperature for 5 hours and then at 10° C. for 2 hours. Then, the crystal precipitated was filtered, and the filter cake was washed with cold MIBK (30 ml) and dried to give a diastereomer salt (8.76 g) of (S)-(+)-2-(3-benzoylphenyl)propionic acid with (S)-(+)-3-methyl-2-phenylbutylamine. The yield of the product based on (S)-(+)-2-(3-benzoylphenyl)propionic acid contained in the starting material was 84%. dissolved the addition the reaction solution was stirred at 35° C. to 40° C. for one hour at 10° C. for 2 hours Then, the crystal precipitated was filtered the filter cake was washed with cold MIBK (30 ml) dried

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (±)-2-(3-Benzoylphenyl)propionic acid (20.3 g, 80 mmol) was dissolved in methyl isobutyl ketone (hereinafter abbreviated to "MIBK") (90 g) with heating. Then, (S)-(+)-3-methyl-2-phenylbutylamine (6.68 g, 41 mmol) was added dropwise with stirring at 40° C. After completing the addition, the reaction solution was stirred at 40° C. for one hour and then cooled slowly to 10° C. over 6 hours. After stirring at 10° C. for 3 hours, the precipitated crystal was filtered and the filter cake was washed with cold MIBK (50 ml) and then dried. In this manner, a diastereomer salt (11.5 g) of (S)-(+)-2-(3-benzoylphenyl)propionic acid with (S)-(+)-3-methyl-2-phenylbutylamine was obtained. with heating the addition the reaction solution was stirred at 40° C. for one hour cooled slowly to 10° C. over 6 hours After stirring at 10° C. for 3 hours the precipitated crystal was filtered the filter cake was washed with cold MIBK (50 ml) dried