tert-butyl N-[(2R)-1-hydroxy-3-methoxypropan-2-yl]carbamate

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

Procedure: To a stirred solution of tert-butyl [(2R)-1-hydroxy-3-methoxypropan-2-yl]carbamate (synthesized according to the procedure described in Sowinski, J. A.; Toogood, P. L. J. Org. Chem. (1996), 61(22), 7671-7676) (8.3 g, 40.4 mmol) tetrahydrofuran (100 mL), 1M solution of potassium t-butoxide in tetrahydrofuran (80.9 mL, 80.9 mmol) was added dropwise at 0° C. and the mixture was stirred at the room temperature for 2 hours. Water (20 ml) was added to the reaction mixture and extracted with ethyl acetate (3×50 ml). The combined organic layers were washed with brine and dried over Na2SO4. Yield: 5.0 g (94%). 1H NMR (300 MHz, DMSO-d6) δ: 3.3 (s, 3H), 3.3 (m, 2H), 3.9 (m, 1H), 4.0 (dd, 1H), 4.3 (t, 1H), 7.7 (d, 1H). [α]D25=−5.876. extracted with ethyl acetate (3×50 ml) The combined organic layers were washed with brine dried over Na2SO4

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

Procedure: To a stirred solution of tert-butyl[(2R)-1-hydroxy-3-methoxypropan-2-yl]carbamate (synthesized according to the procedure described in Sowinski, J. A.; Toogood, P. L. J. Org. Chem. (1996), 61(22), 7671-7676) (8.3 g, 40.4 mmol) tetrahydrofuran (100 mL), 1M solution of potassium t-butoxide in tetrahydrofuran (80.9 mL, 80.9 mmol) was added dropwise at 0° C. and the mixture was stirred at the room temperature for 2 hours. Water (20 ml) was added to the reaction mixture and extracted with ethyl acetate (3×50 ml). The combined organic layers were washed with brine and dried over Na2SO4. Yield: 5.0 g (94%). 1H NMR (300 MHz, DMSO-d6) δ: 3.3 (s, 3H), 3.3 (m, 2H), 3.9 (m, 1H), 4.0 (dd, 1H), 4.3 (t, 1H), 7.7 (d, 1H). [α]D25=−5.876. extracted with ethyl acetate (3×50 ml) The combined organic layers were washed with brine dried over Na2SO4

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

Procedure: Methanesulfonyl chloride (4.0 g, 35 mmol) in DCM (50 mL) was slowly added to a solution of (R)-tert-butyl 1-hydroxy-3-methoxypropan-2-ylcarbamate (6.0 g, 29 mmol) and Et3N (3.64 g, 36 mmol) in DCM (150 mL) at 0° C. The reaction mixture was stirred at RT for 2 h. The organic phase was washed with water and saturated aq NaHCO3, concentrated, and dissolved in DMF. Sodium azide (2.34 g, 36.0 mmol) was added, and the reaction mixture was stirred at 75° C. for 4 h. The reaction mixture was diluted by EtOAc and washed with water. The crude product was purified by column chromatography on silica gel eluting with EtOAc and petroleum ether (EtOAc/PE=2/1) to give the title compound (4.3 g, 64%). 1H NMR (400 MHz, CDCl3) δ ppm 4.92 (s, 1H), 3.91 (m, 1H), 3.53-3.48 (m, 2H), 3.45-3.40 (m, 2H), 3.38 (s, 3H), 1.47 (s, 9H). The organic phase was washed with water and saturated aq NaHCO3 concentrated dissolved in DMF the reaction mixture was stirred at 75° C. for 4 h washed with water The crude product was purified by column chromatography on silica gel eluting with EtOAc and petroleum ether (EtOAc/PE=2/1)

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of (S)-2-(tert-butoxycarbonylamino)-3-methoxypropanoic acid (10.9 g) and N-methylmorpholine (5.6 g, 55 mmol) in THF (50 mL) was added 2-methylpropylchloroformate (7.48 g, 55 mmol) in THF at −15° C. The reaction mixture was stirred −15° C. for 15 min, after which NaBH4 (6.0 g, 159 mmol) in water (10 mL) was added. The reaction mixture was stirred for 30 min, then diluted with EtOAc, and neutralized with dilute HCl. The organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel eluting with EtOAc and petroleum ether (EtOAc/PE=1.5/1) to give the title compound (6.0 g, 58%). 1H NMR (400 MHz, CDCl3) δ ppm 5.23 (s, 1H), 3.80 (d, J=8.0 Hz, 2H), 3.72-3.68 (m, 1H), 3.60-3.52 (m, 2H), 3.38 (s, 3H), 2.85 (s, 1H), 1.47 (s, 9H). The reaction mixture was stirred for 30 min The organic layer was dried over Na2SO4 concentrated The residue was purified by column chromatography on silica gel eluting with EtOAc and petroleum ether (EtOAc/PE=1.5/1)

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

Procedure: Methanesulfonyl chloride (4.0 g, 35 mmol) in DCM (50 mL) was slowly added to a solution of (R)-tert-butyl 1-hydroxy-3-methoxypropan-2-ylcarbamate (6.0 g, 29 mmol) and Et3N (3.64 g, 36 mmol) in DCM (150 mL) at 0° C. The reaction mixture was stirred at RT for 2 h. The organic phase was washed with water and saturated aq NaHCO3, concentrated, and dissolved in DMF. Sodium azide (2.34 g, 36.0 mmol) was added, and the reaction mixture was stirred at 75° C. for 4 h. The reaction mixture was diluted by EtOAc and washed with water. The crude product was purified by column chromatography on silica gel eluting with EtOAc and petroleum ether (EtOAc/PE=2/1) to give the title compound (4.3 g, 64%). 1H NMR (400 MHz, CDCl3) δ ppm 4.92 (s, 1 H), 3.91 (m, 1 H), 3.53-3.48 (m, 2 H), 3.45-3.40 (m, 2 H), 3.38 (s, 3 H), 1.47 (s, 9 H). The organic phase was washed with water and saturated aq NaHCO3 concentrated dissolved in DMF the reaction mixture was stirred at 75° C. for 4 h washed with water The crude product was purified by column chromatography on silica gel eluting with EtOAc and petroleum ether (EtOAc/PE=2/1)

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of (S)-2-(tert-butoxycarbonylamino)-3-methoxypropanoic acid (10.9 g) and N-methylmorpholine (5.6 g, 55 mmol) in THF (50 mL) was added 2-methylpropylchloroformate (7.48 g, 55 mmol) in THF at −15° C. The reaction mixture was stirred −15° C. for 15 min, after which NaBH4 (6.0 g, 159 mmol) in water (10 mL) was added. The reaction mixture was stirred for 30 min, then diluted with EtOAc, and neutralized with dilute HCl. The organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel eluting with EtOAc and petroleum ether (EtOAc/PE=1.5/1) to give the title compound (6.0 g, 58%). 1H NMR (400 MHz, CDCl3) δ ppm 5.23 (s, 1 H), 3.80 (d, J=8.0 Hz, 2 H), 3.72-3.68 (m, 1 H), 3.60-3.52 (m, 2 H), 3.38 (s, 3 H), 2.85 (s, 1 H), 1.47 (s, 9H). The reaction mixture was stirred for 30 min The organic layer was dried over Na2SO4 concentrated The residue was purified by column chromatography on silica gel eluting with EtOAc and petroleum ether (EtOAc/PE=1.5/1)

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

Procedure: To a stirred solution of tert-butyl [(2R)-1-hydroxy-3-methoxypropan-2-yl]carbamate (synthesized according to the procedure described in Sowinski, J. A.; Toogood, P. L. J. Org. Chem. (1996), 61(22), 7671-7676) (8.3 g, 40.4 mmol) tetrahydrofuran (100 mL), 1M solution of potassium t-butoxide in tetrahydrofuran (80.9 mL, 80.9 mmol) was added dropwise at 0° C. and the mixture was stirred at the room temperature for 2 hours. Water (20 ml) was added to the reaction mixture and extracted with ethyl acetate (3×50 ml). The combined organic layers were washed with brine and dried over Na2SO4. Yield: 5.0 g (94%). 1H NMR (300 MHz, DMSO-d6) δ: 3.3 (s, 3H), 3.3 (m, 2H), 3.9 (m, 1H), 4.0 (dd, 1H), 4.3 (t, 1H), 7.7 (d, 1H). [α]D25=−5.876. extracted with ethyl acetate (3×50 ml) The combined organic layers were washed with brine dried over Na2SO4

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

Procedure: To a stirred solution of tert-butyl [(2R)-1-hydroxy-3-methoxypropan-2-yl]carbamate (synthesized according to the procedure described in Sowinski, J. A.; Toogood, P. L. J. Org. Chem. (1996), 61(22), 7671-7676) (8.3 g, 40.4 mmol) tetrahydrofuran (100 mL), 1M solution of potassium t-butoxide in tetrahydrofuran (80.9 mL, 80.9 mmol) was added dropwise at 0° C. and the mixture was stirred at the room temperature for 2 hours. Water (20 ml) was added to the reaction mixture and extracted with ethyl acetate (3×50 ml). The combined organic layers were washed with brine and dried over Na2SO4. Yield: 5.0 g (94%). 1H NMR (300 MHz, DMSO-d6) δ: 3.3 (s, 3H), 3.3 (m, 2H), 3.9 (m, 1H), 4.0 (dd, 1H), 4.3 (t, 1H), 7.7 (d, 1H). [α]D25=−5.876. extracted with ethyl acetate (3×50 ml) The combined organic layers were washed with brine dried over Na2SO4

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

Procedure: Methanesulfonyl chloride (4.0 g, 35 mmol) in DCM (50 mL) was slowly added to a solution of (R)-tert-butyl 1-hydroxy-3-methoxypropan-2-ylcarbamate (6.0 g, 29 mmol) and Et3N (3.64 g, 36 mmol) in DCM (150 mL) at 0° C. The reaction mixture was stirred at RT for 2 h. The organic phase was washed with water and saturated aq NaHCO3, concentrated, and dissolved in DMF. Sodium azide (2.34 g, 36.0 mmol) was added, and the reaction mixture was stirred at 75° C. for 4 h. The reaction mixture was diluted by EtOAc and washed with water. The crude product was purified by column chromatography on silica gel eluting with EtOAc and petroleum ether (EtOAc/PE=2/1) to give the title compound (4.3 g, 64%). 1H NMR (400 MHz, CDCl3) δ ppm 4.92 (s, 1H), 3.91 (m, 1H), 3.53-3.48 (m, 2H), 3.45-3.40 (m, 2H), 3.38 (s, 3H), 1.47 (s, 9H). The organic phase was washed with water and saturated aq NaHCO3 concentrated dissolved in DMF the reaction mixture was stirred at 75° C. for 4 h washed with water The crude product was purified by column chromatography on silica gel eluting with EtOAc and petroleum ether (EtOAc/PE=2/1)

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

Procedure: Methanesulfonyl chloride (4.0 g, 35 mmol) in DCM (50 mL) was slowly added to a solution of (R)-tert-butyl 1-hydroxy-3-methoxypropan-2-ylcarbamate (6.0 g, 29 mmol) and Et3N (3.64 g, 36 mmol) in DCM (150 mL) at 0° C. The reaction mixture was stirred at RT for 2 h. The organic phase was washed with water and saturated aq NaHCO3, concentrated, and dissolved in DMF. Sodium azide (2.34 g, 36.0 mmol) was added, and the reaction mixture was stirred at 75° C. for 4 h. The reaction mixture was diluted by EtOAc and washed with water. The crude product was purified by column chromatography on silica gel eluting with EtOAc and petroleum ether (EtOAc/PE=2/1) to give the title compound (4.3 g, 64%). 1H NMR (400 MHz, CDCl3) δ ppm 4.92 (s, 1H), 3.91 (m, 1H), 3.53-3.48 (m, 2H), 3.45-3.40 (m, 2H), 3.38 (s, 3H), 1.47 (s, 9H). The organic phase was washed with water and saturated aq NaHCO3 concentrated dissolved in DMF the reaction mixture was stirred at 75° C. for 4 h washed with water The crude product was purified by column chromatography on silica gel eluting with EtOAc and petroleum ether (EtOAc/PE=2/1)

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of (S)-2-(tert-butoxycarbonylamino)-3-methoxypropanoic acid (10.9 g) and N-methylmorpholine (5.6 g, 55 mmol) in THF (50 mL) was added 2-methylpropylchloroformate (7.48 g, 55 mmol) in THF at −15° C. The reaction mixture was stirred −15° C. for 15 min, after which NaBH4 (6.0 g, 159 mmol) in water (10 mL) was added. The reaction mixture was stirred for 30 min, then diluted with EtOAc, and neutralized with dilute HCl. The organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel eluting with EtOAc and petroleum ether (EtOAc/PE=1.5/1) to give the title compound (6.0 g, 58%). 1H NMR (400 MHz, CDCl3) δ ppm 5.23 (s, 1H), 3.80 (d, J=8.0 Hz, 2H), 3.72-3.68 (m, 1H), 3.60-3.52 (m, 2H), 3.38 (s, 3H), 2.85 (s, 1H), 1.47 (s, 9H). The reaction mixture was stirred for 30 min The organic layer was dried over Na2SO4 concentrated The residue was purified by column chromatography on silica gel eluting with EtOAc and petroleum ether (EtOAc/PE=1.5/1)

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

Procedure: To a stirred solution of tert-butyl[(2R)-1-hydroxy-3-methoxypropan-2-yl]carbamate (synthesized according to the procedure described in Sowinski, J. A.; Toogood, P. L. J. Org. Chem. (1996), 61(22), 7671-7676) (8.3 g, 40.4 mmol) tetrahydrofuran (100 mL), 1M solution of potassium t-butoxide in tetrahydrofuran (80.9 mL, 80.9 mmol) was added dropwise at 0° C. and the mixture was stirred at the room temperature for 2 hours. Water (20 ml) was added to the reaction mixture and extracted with ethyl acetate (3×50 ml). The combined organic layers were washed with brine and dried over Na2SO4. Yield: 5.0 g (94%). 1H NMR (300 MHz, DMSO-d6) δ: 3.3 (s, 3H), 3.3 (m, 2H), 3.9 (m, 1H), 4.0 (dd, 1H), 4.3 (t, 1H), 7.7 (d, 1H). [α]D25=−5.876. extracted with ethyl acetate (3×50 ml) The combined organic layers were washed with brine dried over Na2SO4