benzyl 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 solution of benzyl [(2R)-1-hydroxy-3-methoxypropan-2-yl]carbamate (30 g, 0.13 mol) in DCM (300 mL) at 0° C. was added triethylamine (19.0 g, 0.188 mol) and methanesulfonylchloride (21.6 g, 0.188 mol) and then the reaction mixture was allowed to warm to ambient temperature. After 16 hours, the reaction mixture was washed with brine, and the organics were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified via chromatography on silica gel (10% ethyl acetate/petroleum ether) to give (2S)-2-{[(benzyloxy)carbonyl]amino}-3-methoxypropyl methanesulfonate. MS ESI calc'd. for C13H20NO6S [M+H]+ 318. found 318. 1H NMR (400 MHz, CDCl3) δ 7.36-7.33 (m, 5H), 5.24 (d, J=8.0 Hz, 1H), 5.10 (s, 2H), 4.28 (d, J=5.6 Hz, 2H), 4.12-4.09 (m, 1H), 3.55-3.42 (m, 2H), 3.35 (s, 3H), 2.99 (s, 3H). the reaction mixture was washed with brine the organics were dried over sodium sulfate concentrated under reduced pressure The residue was purified via chromatography on silica gel (10% ethyl acetate/petroleum ether)

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

Procedure: To a solution of methyl N-[(benzyloxy)carbonyl]-O-methyl-L-serinate (60 g, 0.22 mol) in methanol (600 mL) was added lithium borohydride (39.2 g, 1.80 mol). After 2 hours, the reaction mixture was quenched with saturated aqueous ammonium chloride solution, partially concentrated under reduced pressure, and diluted with water. The mixture was extracted with ethyl acetate (3×100 mL), and the combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified via chromatography on silica gel to give benzyl [(2R)-1-hydroxy-3-methoxypropan-2-yl]carbamate. MS ESI calc'd. for C12H18NO4 [M+H]+ 240. found 240. 1H NMR (400 MHz, CDCl3) δ 7.56-7.30 (m, 5H), 5.52 (br s, 1H), 5.08 (s, 2H), 3.84 (d, J=16.0 Hz, 2H), 3.76-3.64 (m, 1H), 3.63-3.52 (m, 2H), 3.38 (s, 3H), 2.55 (bs, 1H). the reaction mixture was quenched with saturated aqueous ammonium chloride solution partially concentrated under reduced pressure diluted with water The mixture was extracted with ethyl acetate (3×100 mL) the combined organic layers were dried over sodium sulfate concentrated under reduced pressure The residue was purified via chromatography on silica gel

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

Procedure: To a solution of methyl N-[(benzyloxy)carbonyl]-O-methyl-L-serinate (60 g, 0.22 mol) in methanol (600 mL) was added lithium borohydride (39.2 g, 1.80 mol). After 2 hours, the reaction mixture was quenched with saturated aqueous ammonium chloride solution, partially concentrated under reduced pressure, and diluted with water. The mixture was extracted with ethyl acetate (3×100 mL), and the combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified via chromatography on silica gel to give benzyl [(2R)-1-hydroxy-3-methoxypropan-2-yl]carbamate. MS ESI calc'd. for C12H18NO4 [M+H]+ 240. found 240. 1H NMR (400 MHz, CDCl3) δ 7.56-7.30 (m, 5H), 5.52 (br s, 1H), 5.08 (s, 2H), 3.84 (d, J=16.0 Hz, 2H), 3.76-3.64 (m, 1H), 3.63-3.52 (m, 2H), 3.38 (s, 3H), 2.55 (bs, 1H). the reaction mixture was quenched with saturated aqueous ammonium chloride solution partially concentrated under reduced pressure diluted with water The mixture was extracted with ethyl acetate (3×100 mL) the combined organic layers were dried over sodium sulfate concentrated under reduced pressure The residue was purified via chromatography on silica gel

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Calcium chloride (16.63 g, 149.8 mmol) is added to a stirring suspension of sodium borohydride (11.33 g, 299.6 mmol) in ethanol (300 mL) at −40° C. The heterogeneous mixture is warmed to −20° C. and stirred for 1 h. (S)-2-Benzyloxycarbonylamino-3-methoxy-propionic acid methyl ester (20 g, 74.9 mmol) in abs EtOH (250 mL) is then added via cannula transfer. The heterogeneous mixture is stirred at −20° C. for 3 h. The reaction is quenched with water (400 mL) and carefully acidified with 1.0 M HCl. The aqueous layer is extracted with CH2Cl2 (4×200 mL) and the combined organic phases are washed with brine (200 mL), dried over anhydrous Na2SO4 and concentrated to afford a colorless oil. The mixture is absorbed onto the silica gel and chromatographed on silica gel (hexane:EtOAc, 4:1>2:1>1:1>1:2) to afford 11.5 g (64%) of (R)-(1-hydroxymethyl-2-methoxy-ethyl)-carbamic acid benzyl ester as a colorless oil. is then added via cannula transfer The reaction is quenched with water (400 mL) The aqueous layer is extracted with CH2Cl2 (4×200 mL) the combined organic phases are washed with brine (200 mL) dried over anhydrous Na2SO4 concentrated to afford a colorless oil The mixture is absorbed onto the silica gel chromatographed on silica gel (hexane:EtOAc, 4:1>2:1>1:1>1:2)

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

Procedure: To a solution of benzyl [(2R)-1-hydroxy-3-methoxypropan-2-yl]carbamate (30 g, 0.13 mol) in DCM (300 mL) at 0° C. was added triethylamine (19.0 g, 0.188 mol) and methanesulfonylchloride (21.6 g, 0.188 mol) and then the reaction mixture was allowed to warm to ambient temperature. After 16 hours, the reaction mixture was washed with brine, and the organics were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified via chromatography on silica gel (10% ethyl acetate/petroleum ether) to give (2S)-2-{[(benzyloxy)carbonyl]amino}-3-methoxypropyl methanesulfonate. MS ESI calc'd. for C13H20NO6S [M+H]+ 318. found 318. 1H NMR (400 MHz, CDCl3) δ 7.36-7.33 (m, 5H), 5.24 (d, J=8.0 Hz, 1H), 5.10 (s, 2H), 4.28 (d, J=5.6 Hz, 2H), 4.12-4.09 (m, 1H), 3.55-3.42 (m, 2H), 3.35 (s, 3H), 2.99 (s, 3H). the reaction mixture was washed with brine the organics were dried over sodium sulfate concentrated under reduced pressure The residue was purified via chromatography on silica gel (10% ethyl acetate/petroleum ether)

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

Procedure: To a solution of methyl N-[(benzyloxy)carbonyl]-O-methyl-L-serinate (60 g, 0.22 mol) in methanol (600 mL) was added lithium borohydride (39.2 g, 1.80 mol). After 2 hours, the reaction mixture was quenched with saturated aqueous ammonium chloride solution, partially concentrated under reduced pressure, and diluted with water. The mixture was extracted with ethyl acetate (3×100 mL), and the combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified via chromatography on silica gel to give benzyl [(2R)-1-hydroxy-3-methoxypropan-2-yl]carbamate. MS ESI calc'd. for C12H18NO4 [M+H]+ 240. found 240. 1H NMR (400 MHz, CDCl3) δ 7.56-7.30 (m, 5H), 5.52 (br s, 1H), 5.08 (s, 2H), 3.84 (d, J=16.0 Hz, 2H), 3.76-3.64 (m, 1H), 3.63-3.52 (m, 2H), 3.38 (s, 3H), 2.55 (bs, 1H). the reaction mixture was quenched with saturated aqueous ammonium chloride solution partially concentrated under reduced pressure diluted with water The mixture was extracted with ethyl acetate (3×100 mL) the combined organic layers were dried over sodium sulfate concentrated under reduced pressure The residue was purified via chromatography on silica gel