tert-butyl 4-hydroxy-2-(hydroxymethyl)pyrrolidine-1-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of 4-hydroxy-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (10.85 g, 50.0 mmol) in pyridine (50 mL) was added methanesulfonyl chloride (10.8 mL, 140 mmol) over a period of 20 min. After stirring for 16 h, the reaction mixture was concentrated to dryness, diluted with satd. aq. Na2CO3 and extracted with EtOAc (2×). The combined organic layers were dried (MgSO4), filtered and concentrated to provide the title compound as an oil that slowly solidified (14.4 g, 84%). 1H NMR (400 MHz, CDCl3): 5.24-5.20 (m, 1H), 4.72-4.47 (m, 1H), 4.32-4.17 (m, 2H), 4.01-3.75 (m, 1H), 3.63-3.48 (m, 1H), 3.04 (s, 3H), 3.01 (s, 3H), 2.60-2.25 (m, 2H), 1.48 (s, 9H). the reaction mixture was concentrated to dryness diluted with satd aq. Na2CO3 and extracted with EtOAc (2×) The combined organic layers were dried (MgSO4) filtered concentrated

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of 4-hydroxy-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (10.85 g, 50.0 mmol) in pyridine (50 mL) was added methanesulfonyl chloride (10.8 mL, 140 mmol) over a period of 20 min. After stirring for 16 h, the reaction mixture was concentrated to dryness, diluted with satd. aq. Na2CO3 and extracted with EtOAc (2×). The combined organic layers were dried (MgSO4), filtered and concentrated to provide the title compound as an oil that slowly solidified (14.4 g, 84%). 1H NMR (400 MHz, CDCl3): 5.24-5.20 (m, 1H), 4.72-4.47 (m, 1H), 4.32-4.17 (m, 2H), 4.01-3.75 (m, 1H), 3.63-3.48 (m, 1H), 3.04 (s, 3H), 3.01 (s, 3H), 2.60-2.25 (m, 2H), 1.48 (s, 9H). the reaction mixture was concentrated to dryness diluted with satd aq. Na2CO3 and extracted with EtOAc (2×) The combined organic layers were dried (MgSO4) filtered concentrated

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

Procedure: To a solution of 4-hydroxy-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (10.85 g, 50.0 mmol) in pyridine (50 mL) was added methanesulfonyl chloride (10.8 mL, 140 mmol) over a period of 20 min. After stirring for 16 h, the reaction mixture was concentrated to dryness, diluted with satd. aq. Na2CO3 and extracted with EtOAc (2×). The combined organic layers were dried (MgSO4), filtered and concentrated to provide the title compound as an oil that slowly solidified (14.4 g, 84%). 1H NMR (400 MHz, CDCl3): 5.24-5.20 (m, 1H), 4.72-4.47 (m, 1H), 4.32-4.17 (m, 2H), 4.01-3.75 (m, 1H), 3.63-3.48 (m, 1H), 3.04 (s, 3H), 3.01 (s, 3H), 2.60-2.25 (m, 2H), 1.48 (s, 9H). the reaction mixture was concentrated to dryness diluted with satd aq. Na2CO3 and extracted with EtOAc (2×) The combined organic layers were dried (MgSO4) filtered concentrated

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

Procedure: To a solution of 4-hydroxy-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (10.85 g, 50.0 mmol) in pyridine (50 mL) was added methanesulfonyl chloride (10.8 mL, 140 mmol) over a period of 20 min. After stirring for 16 h, the reaction mixture was concentrated to dryness, diluted with satd. aq. Na2CO3 and extracted with EtOAc (2×). The combined organic layers were dried (MgSO4), filtered and concentrated to provide the title compound as an oil that slowly solidified (14.4 g, 84%). 1H NMR (400 MHz, CDCl3): 5.24-5.20 (m, 1H), 4.72-4.47 (m, 1H), 4.32-4.17 (m, 2H), 4.01-3.75 (m, 1H), 3.63-3.48 (m, 1H), 3.04 (s, 3H), 3.01 (s, 3H), 2.60-2.25 (m, 2H), 1.48 (s, 9H). the reaction mixture was concentrated to dryness diluted with satd aq. Na2CO3 and extracted with EtOAc (2×) The combined organic layers were dried (MgSO4) filtered concentrated

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of 4-hydroxy-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (10.85 g, 50.0 mmol) in pyridine (50 mL) was added methanesulfonyl chloride (10.8 mL, 140 mmol) over a period of 20 min. After stirring for 16 h, the reaction mixture was concentrated to dryness, diluted with satd. aq. Na2CO3 and extracted with EtOAc (2×). The combined organic layers were dried (MgSO4), filtered and concentrated to provide the title compound as an oil that slowly solidified (14.4 g, 84%). 1H NMR (400 MHz, CDCl3): 5.24-5.20 (m, 1H), 4.72-4.47 (m, 1H), 4.32-4.17 (m, 2H), 4.01-3.75 (m, 1H), 3.63-3.48 (m, 1H), 3.04 (s, 3H), 3.01 (s, 3H), 2.60-2.25 (m, 2H), 1.48 (s, 9H). the reaction mixture was concentrated to dryness diluted with satd aq. Na2CO3 and extracted with EtOAc (2×) The combined organic layers were dried (MgSO4) filtered concentrated

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

Procedure: To a stirred solution of the diol (344) (12.7 g, 58.5 mmol) and triethylamine (5 equiv., 41 mL) in CH2Cl2 (200 mL) at 0° C. was added methanesulfonyl chloride (NsCl) (2.4 equiv., 10.9 mL). The resulting suspension was removed from the ice bath and allowed to warm to room temperature with stirring at which point TLC analysis indicated complete consumption of the starting material and conversion to a single spot of higher Rf (5% MeOH/CHCl3, stained with K2MnO4). The reaction was quenched by the addition of water (20 mL) with vigorous stirring. NaHCO3 (sat., aqueous, 200 mL) was added and the organic layer was separated, washed with brine, dried (MgSO4) and purified by flash chromatography (1–10% MeOH/CHCl3) to yield the desired compound (345) as a colorless oil. The resulting suspension was removed from the ice bath consumption of the starting material and conversion to a single spot of higher Rf (5% MeOH/CHCl3, stained with K2MnO4) The reaction was quenched by the addition of water (20 mL) with vigorous stirring NaHCO3 (sat., aqueous, 200 mL) was added the organic layer was separated washed with brine dried (MgSO4) purified by flash chromatography (1–10% MeOH/CHCl3)