(2R)-2-amino-N-benzyl-3-methoxypropanamide

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-benzyl-O-methyl-D-serinamide (5 g), was mixed with DCM (25 ml) at ambient temperature and stirred for 10 minutes to get a clear solution. To this solution, dimethylaminopyridine (0.025 g) was added at ambient temperature. Acetic anhydride (2.695 g) was slowly added over 10-12 minutes at ambient temperature. The solution was stirred for 30 minutes at room temperature. The reaction mixture was washed with 5% sodium bicarbonate (15 ml) solution, deionized water (15 ml), and brine (10 ml). The layers were separated and solvent was completely recovered under vacuum at 35-40° C. to get crude product. Yield=5.9 gm. to get a clear solution The solution was stirred for 30 minutes at room temperature The reaction mixture was washed with 5% sodium bicarbonate (15 ml) solution The layers were separated solvent was completely recovered under vacuum at 35-40° C. to get crude product

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-benzyl-O-methyl-D-serinamide (92 g), was mixed with dichloromethane (368 ml) at ambient temperature and stirred for 10 minutes to get a clear solution. To this solution, dimethylaminopyridine (0.47 g) was added at ambient temperature. Acetic anhydride (45.09 g) was slowly added over 15-20 minutes at ambient temperature. The solution was stirred for 2 hours at room temperature. The reaction mixture was washed with sodium hydroxide (19.16 gm dissolved in 291 ml water), and deionized water (276 ml). The layers were separated and solvent was completely recovered under vacuum at 35-40° C. to get crude product. Yield=82.6 gm; Chiral purity=100%. to get a clear solution The solution was stirred for 2 hours at room temperature The reaction mixture was washed with sodium hydroxide (19.16 gm dissolved in 291 ml water), and deionized water (276 ml) The layers were separated solvent was completely recovered under vacuum at 35-40° C. to get crude product

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of Example 3 product (i.e., N-benzyl-O-methyl-N2-trityl-D-serinamide, 50 g) in absolute ethanol (100 ml), acetic acid (1.25 mole eq.) was added at room temperature. This solution was stirred for 30 minutes at room temperature and then the solvent was completely recovered under vacuum at 40° C. Water (250 ml) was added to it at room temperature and the aqueous layer was neutralized with aqueous ammonia (20 ml). The aqueous layer was extracted with toluene (2×200 ml). The toluene was then completely recovered under vacuum at 50-55° C. to get an oil. Yield=18 gm. the solvent was completely recovered under vacuum at 40° C Water (250 ml) was added to it at room temperature The aqueous layer was extracted with toluene (2×200 ml) The toluene was then completely recovered under vacuum at 50-55° C. to get an oil

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of Example 3 product (i.e. N-benzyl-O-methyl-N2-trityl-D-serinamide, 50 g) in dichloromethane (100 ml), hydrochloric acid (36%) was added at room temperature. This solution was stirred for 30 minutes at room temperature and then the solvent was completely recovered under vacuum at 40° C. Water (250 ml) was added to it at room temperature and the aqueous layer was neutralized with aqueous ammonia (20 ml). The aqueous layer was extracted with toluene (2×200 ml). The toluene was then completely recovered under vacuum at 50-55° C. to get an oil. Yield=15 gm. the solvent was completely recovered under vacuum at 40° C Water (250 ml) was added to it at room temperature The aqueous layer was extracted with toluene (2×200 ml) The toluene was then completely recovered under vacuum at 50-55° C. to get an oil

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-benzyl-O-methyl-D-serinamide (5 g), was mixed with DCM (25 ml) at ambient temperature and stirred for 10 minutes to get a clear solution. To this solution, dimethylaminopyridine (0.025 g) was added at ambient temperature. Acetic anhydride (2.695 g) was slowly added over 10-12 minutes at ambient temperature. The solution was stirred for 30 minutes at room temperature. The reaction mixture was washed with 5% sodium bicarbonate (15 ml) solution, deionized water (15 ml), and brine (10 ml). The layers were separated and solvent was completely recovered under vacuum at 35° C. to 40° C. to get crude product. Yield=5.9 gm. to get a clear solution The solution was stirred for 30 minutes at room temperature The reaction mixture was washed with 5% sodium bicarbonate (15 ml) solution The layers were separated solvent was completely recovered under vacuum at 35° C. to 40° C. to get crude product

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-benzyl-O-methyl-D-serinamide (92 g), was mixed with dichloromethane (368 ml) at ambient temperature and stirred for 10 minutes to get a clear solution. To this solution, dimethylaminopyridine (0.47 g) was added at ambient temperature. Acetic anhydride (45.09 g) was slowly added over 15-20 minutes at ambient temperature. The solution was stirred for 2 hours at room temperature. The reaction mixture was washed with sodium hydroxide (19.16 gm dissolved in 291 ml water), and deionized water (276 ml). The layers were separated and solvent was completely recovered under vacuum at 35° C. to 40° C. to get crude product. Yield=82.6 gm; Chiral purity=100%. to get a clear solution The solution was stirred for 2 hours at room temperature The reaction mixture was washed with sodium hydroxide (19.16 gm dissolved in 291 ml water), and deionized water (276 ml) The layers were separated solvent was completely recovered under vacuum at 35° C. to 40° C. to get crude product

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of Example 3 product (i.e., N-benzyl-O-methyl-N2-trityl-D-serinamide, 50 g) in absolute ethanol (100 ml), acetic acid (1.25 mole eq.) was added at room temperature. This solution was stirred for 30 minutes at room temperature and then the solvent was completely recovered under vacuum at 40° C. Water (250 ml) was added to it at room temperature and the aqueous layer was neutralized with aqueous ammonia (20 ml). The aqueous layer was extracted with toluene (2×200 ml). The toluene was then completely recovered under vacuum at 50° C. to 55° C. to get an oil. Yield=18 gm. the solvent was completely recovered under vacuum at 40° C Water (250 ml) was added to it at room temperature The aqueous layer was extracted with toluene (2×200 ml) The toluene was then completely recovered under vacuum at 50° C. to 55° C. to get an oil

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of Example 3 product (i.e. N-benzyl-O-methyl-N2-trityl-D-serinamide, 50 g) in dichloromethane (100 ml), hydrochloric acid (36%) was added at room temperature. This solution was stirred for 30 minutes at room temperature and then the solvent was completely recovered under vacuum at 40° C. Water (250 ml) was added to it at room temperature and the aqueous layer was neutralized with aqueous ammonia (20 ml). The aqueous layer was extracted with toluene (2×200 ml). The toluene was then completely recovered under vacuum at 50° C. to 55° C. to get an oil. Yield=15 gm. the solvent was completely recovered under vacuum at 40° C Water (250 ml) was added to it at room temperature The aqueous layer was extracted with toluene (2×200 ml) The toluene was then completely recovered under vacuum at 50° C. to 55° C. to get an oil

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of acetic anhydride (262 mg, 2.56 mmol) and (R)-2-amino-N-benzyl-3-methoxypropanamide 1.6 TFA (1000 mg, 2.56 mmol) in 10 mL of DCM and triethylamine (3.6 mL, 25.6 mmol) was added. The resulting solution was stirred at room temperature for three hours. DCM (200 mL) was added to the reaction mixture. The resulting solution was washed with H2O (200 mL), 0.2 N HCl (100 mL), 5% NaHCO3 (100 mL), and then H2O (100 mL) and dried over Na2SO4. A white solid was obtained after the solvent was removed under reduced pressure. The crude product was purified by crystallization from ethyl acetate/hexane (1:1). The desired product was obtained with a purity of 99% (220 mg, yield: 33.0%). 1H NMR (500 MHz, CDCl3) δ 2.05 (s, 3H). 3.39 (s, 3H), 3.45 (t, 1H), 3.84 (m, 1H), 4.48 (s, 2H), 4.56 (m, 1H), 6.44 (br., 1H). 6.74 (br., 1H), 7.28 (m, 3H), 7.36 (m, 2H). LC-MS (m/z) calculated 250.1. Found 251.1 [M+H]+, 273.1 [M+Na]+. The resulting solution was washed with H2O (200 mL), 0.2 N HCl (100 mL), 5% NaHCO3 (100 mL) H2O (100 mL) and dried over Na2SO4 A white solid was obtained after the solvent was removed under reduced pressure The crude product was purified by crystallization from ethyl acetate/hexane (1:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (R)—N-benzyl-2-Boc-amino-3-methoxypropanamide (9.8 g, 31.8 mmol) was dissolved in 15 mL of DCM and then 15 mL of TFA was added to the solution. The mixture was stirred at room temperature for two hours. The solvent and TFA was removed by evaporation and a white solid was obtained (12.4, 100%). Upon analysis, it was determined that on average each molecule contained 1.6 TFA. 1H NMR (500 MHz, DMSO) δ 3.30 (s, 3H), 3.69 (m, 2H), 4.05 (m, 1H), 4.35 (m, 2H), 7.25 (m, 3H), 7.35 (m, 2H), 8.23 (br., 2H), 8.95 (m, 1H). LC-MS (m/z) calcd. 208.1. Found 209.1 [M+H]+. The solvent and TFA was removed by evaporation a white solid was obtained (12.4, 100%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-benzyl-O-methyl-D-serinamide (5 g), was mixed with DCM (25 ml) at ambient temperature and stirred for 10 minutes to get a clear solution. To this solution, dimethylaminopyridine (0.025 g) was added at ambient temperature. Acetic anhydride (2.695 g) was slowly added over 10-12 minutes at ambient temperature. The solution was stirred for 30 minutes at room temperature. The reaction mixture was washed with 5% sodium bicarbonate (15 ml) solution, deionized water (15 ml), and brine (10 ml). The layers were separated and solvent was completely recovered under vacuum at 35-40° C. to get crude product. Yield=5.9 gm. to get a clear solution The solution was stirred for 30 minutes at room temperature The reaction mixture was washed with 5% sodium bicarbonate (15 ml) solution The layers were separated solvent was completely recovered under vacuum at 35-40° C. to get crude product

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-benzyl-O-methyl-D-serinamide (5 g), was mixed with DCM (25 ml) at ambient temperature and stirred for 10 minutes to get a clear solution. To this solution, dimethylaminopyridine (0.025 g) was added at ambient temperature. Acetic anhydride (2.695 g) was slowly added over 10-12 minutes at ambient temperature. The solution was stirred for 30 minutes at room temperature. The reaction mixture was washed with 5% sodium bicarbonate (15 ml) solution, deionized water (15 ml), and brine (10 ml). The layers were separated and solvent was completely recovered under vacuum at 35-40° C. to get crude product. Yield=5.9 gm. to get a clear solution The solution was stirred for 30 minutes at room temperature The reaction mixture was washed with 5% sodium bicarbonate (15 ml) solution The layers were separated solvent was completely recovered under vacuum at 35-40° C. to get crude product