Methane → (2S,4R)-methyl 1-(2-chloroacetyl)-4-hydroxypyrrolidine-2-carboxylate

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Reaction Steps

To a suspension of Example 19A (130 g, 0.72 mol, 1 equivalent) in benzene (3.9 L), chloroacetyl chloride (81.1 g, 0.72 mol, 1 equivalent) was added dropwise at 20-25° C. The reaction mixture was refluxed for 5 hours. Then, charcoal (500 mg) was added, and the reaction mixture was hot filtered through diatomaceous earth. The filtrate was concentrated under reduced pressure. To this crude material, methyl tert-butyl ether (650 mL) was added, and the mixture was stirred for 30 minutes. The solid was collected by filtration, and the wet cake was dried in a vacuum tray dryer for 5 hours at about 50° C. to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.9-1.96 (m, 1H), 2.08-2.19 (m, 1H), 3.36 (d, 1H, J=14.4 Hz), 3.65 (s, 3H), 3.66 (m, 2H), 4.33 (s, 2H), 4.35 (m, 1H), 5.25 (bs, 1H); MS (ESI) m/z 222 (M+H)+.

Provenance & Evidence