Methyl iodide → tert-butyl N-[(2S)-2-methoxypropyl]carbamate

Participants

Reaction Steps

Cool a solution of tert-butyl [(2S)-2-hydroxypropyl]carbamate (870 g, 4.96 mol) in tetrahydrofuran (10 L) to 5° C. Add sodium hydride (60% dispersion, 248 g, 6.21 mol, 1.25 eq.) in portions over 8 minutes. Stir the reaction at 5° C. for 30 minutes. Add methyl iodide (387 mL, 6.21 mol, 1.25 eq.) dropwise over 5 minutes and allow the reaction to proceed at 5-10° C. for 45 minutes. Quench the reaction with water (1 L) and extract with ethyl acetate (4 L). Obtain the organic layer and concentrate it in vacuo to obtain a residue. Co-evaporate the residue with toluene (2×1 L), dilute with dichloromethane (2 L) and filter. Rinse remaining solid with additional dichloromethane (500 mL). Concentrate the combined dichloromethane liquid filtrate in vacuo to obtain a crude intermediate of tert-butyl N-[(2S)-2-methoxypropyl]carbamate (880 g, 94%).

Provenance & Evidence