methyl 1-methylsulfonylpyrrolidine-2-carboxylate

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

Procedure: Methyl 1-(methylsulfonyl)pyrrolidine-2-carboxylate (1.1 g, 4.6 mmol) in anhydrous tetrahydrofuran (10 mL) was added slowly to a stirring suspension of lithium aluminum hydride (0.259 g, 6.8 mmol) in anhydrous tetrahydrofuran (10 mL) kept at 0° C. with an external ice bath. After fifteen minutes, the ice bath was removed and the reaction was allowed to warm to ambient temperature and stirred for an additional hour. The mixture was cooled to 0° C., and water (1 mL) was added dropwise, followed by 15% aqueous sodium hydroxide (1 mL), and water (3 mL). The mixture was stirred for 15 mins at room temperature, followed by the addition of magnesium sulfate and additional stirring. The mixture was filtered through Celite, washed three times with ether, and the combined organic fractions concentrated under reduced pressure to afford a yellow oil (0.7 g, 77%). 1H NMR (CDCl3, 300 MHz) δ 3.78-3.57 (m, 3H), 3.49-3.36 (m, 2H), 2.87 (s, 3H), 2.64 (br s, 1H), 2.09-1.82 (m, 4H). kept at 0° C. with an external ice bath After fifteen minutes the ice bath was removed The mixture was cooled to 0° C. water (1 mL) was added dropwise The mixture was stirred for 15 mins at room temperature followed by the addition of magnesium sulfate and additional stirring The mixture was filtered through Celite washed three times with ether the combined organic fractions concentrated under reduced pressure

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

Procedure: Methanesulfonyl chloride (2.3 mL, 30 mmol) was slowly added to a stirring solution of D/L-proline methyl ester hydrochloride (5.0 g, 30.2 mmol) and triethylamine (8.4 mL, 60 mmol) in anhydrous methylene chloride (75 mL). The reaction was stirred overnight at ambient temperature and then diluted with ethyl acetate. The organic layer was successively washed with water, 1N aqueous hydrochloric acid twice, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride solutions, dried (anhydrous sodium sulfate), and filtered. The solution was concentrated under reduced pressure to give the desired product as a tan liquid (4.45 g, 72%). 1H NMR (CDCl3, 300 MHz) δ 4.53-4.49 (dd, 1H, J=8.7, 3.6 Hz), 3.75 (s, 3H), 3.57-3.54 (m, 1H), 3.52-3.42 (m, 1H), 3.01 (s, 3H), 2.32-2.22 (m, 1H), 2.11-1.98 (m, 3H). The organic layer was successively washed with water, 1N aqueous hydrochloric acid twice saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride solutions, dried (anhydrous sodium sulfate) filtered The solution was concentrated under reduced pressure