4-Methylmorpholine → Ethyl(5r/s,6r/s)-6-(hydroxymethyl)spiro[2.4]heptane-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

trans-6-(Ethoxycarbonyl)spiro[2.4]heptane-5-carboxylic acid (165 mg, 832 mmol) was placed in a 25 mL round bottom flask. After flushing the flask with nitrogen, tetrahydrofuran (1.6 mL) was added and the reaction mixture was cooled to −78° C. 4-Methylmorpholine (0.11 mL, 1.0 mmol) and isobutyl chloroformate (0.12 mL, 0.93 mmol) were added and the reaction mixture was allowed to warm to ambient temperature. After 15 min., the reaction mixture was recooled to −78° C. and sodium borohydride (60 mg, 1.6 mmol) was added. Methanol (1.3 mL) was added and the reaction mixture was warmed to ambient temperature over 2 h and then quenched with saturated aqueous ammonium chloride. The reaction mixture was diluted with saturated aqueous sodium chloride solution and the product was extracted with ethyl acetate. The combined organics were dried over anhydrous sodium sulfate and then concentrated on a rotary evaporator. Chromatography of the residue on silica gel using 35:65 ethyl acetate:hexanes as eluent provided ethyl(5R/S,6R/S)-6-(hydroxymethyl)spiro[2.4]heptane-5-carboxylate as a colorless oil.

Provenance & Evidence