4-Methylmorpholine → tert-Butyl 3-(hydroxymethyl)azetidine-1-carboxylate

Participants

Reaction Steps

To a solution of 1-Boc-azetidine-3-carboxylic acid (Astatech, 1.0 g, 4.97 mmol) in tetrahydrofuran (10 mL) at −10° C. was added 4-methylmorpholine (0.55 mL, 5.0 mmol). This mixture was stirred for 1 minute and then ethyl chloroformate (0.47 mL, 4.97 mmol) was added dropwise. The mixture was stirred at −10° C. for 15 min then was filtered through Celite and the filtrate was added dropwise via syringe to a mixture of NaBH4 (0.42 g, 111.2 mmol) in H2O (5 mL) at 5° C. The mixture was allowed to warm to ambient temperature and was stirred vigorously for 3 h. The reaction mixture was quenched with 5 mL saturated, aqueous NH4Cl, the layers were separated and the aqueous layer was extracted with 3×5 mL ethyl acetate. The combined organics were dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and purified by column chromatography (SiO2, 30% hexanes in ethyl acetate) to give the title compound (0.62 g, 3.3 mmol, 66% yield). MS (DCI/NH3) m/z 188 (M+H)+.

Provenance & Evidence