Hexamethylphosphoramide → 5-(2-Benzyloxy-ethyl)-2-oxo-cyclohexanecarboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of LDA (33 ml, 1.5 M in Et2O) in THF (50 mL) at −78° C. was treated with 4-(2-benzyloxy-ethyl)-cyclohexanone (9.5 g, 40.2 mmol). The mixture was warmed to 0° C. over 30 minutes before re-cooling to −78° C. and adding HMPA (7 mL). Methyl cyanoformate (4.1 mL, 85 mmol) was added, and the mixture stirred for 15 minutes before aqueous quench and work-up. The product was purified by chromatography on SiO2 with 10% EtOAc:Hx. 5-(2-Benzyloxy-ethyl)-2-oxo-cyclohexanecarboxylic acid methyl ester was isolated, 5.8 g (49%), and reduced with an equivalent of NaBH4 in MeOH at −10° C. The alcohol (Intermediate R2 above) was purified by chromatography on SiO2 with 30 to 50% EtOAC:Hx. (˜90% yield).

Provenance & Evidence