Diethyl Ether → (S)-2-(trimethylsilyl)ethyl 2-amino-3-cyclohexylpropylcarbamate

Participants

Reaction Steps

(S)-tert-butyl 1-(2-(trimethylsilyl)ethoxycarbonylamino)-3-cyclohexylpropan-2-ylcarbamate (8.5 g, 0.0213 mol) was dissolved into a minimal volume of ethyl ether (120 mL) and added to a solution of tosic acid (4.46 g, 0.023 mol) in 25 mL of absolute EtOH. This solution was placed on a rotary evaporator and ethyl ether was removed at ambient temp. The flask was then lowered into the water bath (temperature: 60° C.) and the selective de-protection of the Boc group proceeded concurrently with removal of the remainder of solvent. The reaction was completed by 2 h and gave an off-white solid. This material was cooled to rt and dissolved in 100 mL of a mixture EtOH:H2O (1:1, v/v). This was washed with hexanes:EtOAc (5:1, v/v, 3×12 mL), basified with 1N NaOH (pH>10), and extracted with EtOAc (3×50 mL). The combined organic extracts were washed (3×5 mL 1N NaOH, 3×5 mL brine), dried, decanted and stripped to give the free base of (S)-2-(trimethylsilyl)ethyl 2-amino-3-cyclohexylpropylcarbamate (5.24 g, 82%). 1H NMR (400 MHz, CDCl3): 5.09 (brs, 1H), 4.14 (t, J=8.4 Hz, 2H), 3.23 (m, 1H), 2.88 (m, 2H), 1.75-1.48 (m, 5H), 1.5-0.75 (m, 10H), 0.05 (s, 9H). MS (E/Z): 301 (M+H+).

Provenance & Evidence