Water → tert-butyl N-(3-hydroxy-3-methylcyclobutyl)carbamate

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Reaction Conditions

Reaction Steps

(1-Oxa-spiro[2.3]hex-5-yl)-carbamic acid tert-butyl ester (˜1:1 cis/trans mixture, 3.93 g, 19.7 mmol) was dissolved in anhydrous THF (100 mL) and cooled to 0° C. in an ice/water bath. To this was added a 1.0 M solution of lithium triethylborohydride in THF (25 mL) via dropping addition funnel, over 10 min, then the mixture stirred at 0° C. for 3.5 hours. While still cooled to 0° C., 30 mL deionized water was added dropwise over 5 minutes to quench the reaction. After warming to rt, solid potassium carbonate was added to saturate the aqueous phase, allowing the layers to be separated. The aqueous layer was further extracted with ethyl acetate (2×30 mL). The combined organic layers (THF and EtOAc) were dried over magnesium sulfate, filtered, concentrated, and purified by silica gel chromatography (eluting with 40-80% ethyl acetate in heptanes), affording the title compound (3.16 g, 80%) as a white solid. NMR shows a 55:45 ratio of N,O-cis/trans isomers. 1H NMR (400 MHz, chloroform-d) δ ppm [1.37 (s) and 1.41 (s), 3H together] 1.44 (s, 9H) 1.66 (br. s., 1H) 1.89-2.03 (m, 2H) 2.42-2.54 (m, 2H)

Provenance & Evidence