Tetrahydrofuran → tert-butyl N-(1-(hydroxymethyl)cyclopropyl)carbamate

Participants

Reaction Steps

To a solution of ethyl 1-aminocyclopropanecarboxylate hydrochloride (1 eq) in EtOH (0.3 M) at room temperature was added di-tert-butyl carbonate (1.5 eq), triethylamine (2 eq), and DMAP (0.05 eq). The reaction was stirred at room temperature overnight. The reaction mixture was concentrated en vaccuo; and the residue was diluted in ethyl acetate. The organic solution was washed 1:1 saturated aqueous NH4Cl/water, brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The material was taken up in THF (0.3 M) and cooled to 0° C. To this solution was added 2 M LiBH4 in THF (4 eq). The reaction was warmed to room temperature and stirred for 4 hours, at which time more 2 M LiBH4 (1.3 eq) was added, and stirred overnight. The reaction mixture was cooled to 0° C. and slowly quenched with MeOH over 10 minutes and then water. The solution was stirred for 10 minutes; and precipitates appeared. The precipitates were filtered and rinsed with ethyl acetate. The filtrate was washed with water, brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using a gradient of 0-75% ethyl acetate in hexanes to give the product.

Provenance & Evidence