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

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Reaction Steps

A solution of LDA (33 ml, 1.5 M in Et2O) in THF (50 mL) at −78 EC was treated with 4-(2-benzyloxy-ethyl)-cyclohexanone (9.5 g, 40.2 mmol). The mixture was warmed to 0 EC over 30 m before re-cooling to −78 EC and adding HMPA (7 mL). Methyl cyanoformate (4.1 mL, 85 mmol) was added and the mixture was stirred for 15 m 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 EC to provide the alcohol (Intermediate R2). Intermediate R2 was purified by chromatography on SiO2 with 30 to 50% EtOAC:Hx. (˜90% yield).

Provenance & Evidence