Hydrochloric Acid → tert-Butyl (4-hydroxy-2-methylbutan-2-yl)carbamate

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Reaction Conditions

Reaction Steps

At 0° C., ethyl chloroformate (1.10 ml, 11.5 mmol) was given dropwise to a solution of 3-tert-butoxycarbonylamino-3-methylbutanoic acid (2.50 g, 11.5 mmol) (cf. Schoen et al. J. Med. Chem., 1994, vol. 37, p. 897-906, and references cited herein) and triethylamine (1.92 ml, 13.8 mmol) in tetrahydrofuran (10 ml). The solution was stirred for 40 min at 0° C. The formed precipitate was filtered off and washed with tetrahydrofuran (20 ml). The liquid was immediately cooled to 0° C. A 2M solution of lithium borohydride in tetrahydrofuran (14.4 ml, 28.8 mmol) was added dropwise. The solution was stirred at 0° C. for 2 h, and then warmed to room temperature over a period of 4 h. It was cooled to 0° C. and methanol (5 ml) was added. 1N Hydrochloric acid (100 ml) was added and the solution was extracted with ethyl acetate (2×100 ml, 3×50 ml). The combined organic extracts were washed with saturated sodium hydrogencarbonate solution (100 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was chromatographed on silica (110 g) with ethyl aceteate/heptane (1:2) to give 1.84 g of 3-hydroxy-1,1dimethylpropylcarbamic acid tert-butyl ester.

Provenance & Evidence