Triethylamine → HCID 178453607, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of trans-4-(tert-butoxycarbonylamino-methyl)-cyclohexane-carboxylic acid (155 g, 603 mmol) in CH2Cl2 (1.35 L) was cooled at −65° C. and triethylamine (126 mL, 904 mmol) and a solution of ethyl chloroformate (58 mL, 751 mmol) in CH2Cl2 (200 mL) were added below −60° C. The reaction mixture was stirred at 0° C. for 50 min. The mixture was acidified with saturated aqueous KHSO4 (pH=3), and the aqueous layer was extracted with CHCl3 (three times). The combined organic layer was washed with saturated aqueous Na2CO3 and brine, dried over MgSO4, filtered, and concentrated to give a colorless oil. A solution of the above oil in THF (1.5 L) was cooled at −65° C. and NaBH4 (26.6 g, 703 mmol) and MeOH (45 mL) were added. The mixture was stirred at −40° C. for 25 min, and stirred at 4° C. for 3 hr. The mixture was acidified with saturated aqueous KHSO4 (pH=3), and the aqueous layer was extracted with EtOAc (three times). The combined organic layer was washed with saturated aqueous Na2CO3 and brine, dried over MgSO4, filtered, and concentrated, and purified by flash chromatography (silica gel, 17% MeOH in CHCl3) to give trans-(4-hydroxymethyl-cyclohexylmethyl)-carbamic acid tert-butyl ester (123 g, 84%) as a white solid.

Provenance & Evidence