Hydrochloric Acid → [4-(1-Heptylaminomethyl-cyclopropyl)-phenyl]-methanol

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of the mixture containing 1-(4-hydroxymethyl-phenyl)-cyclopropanecarboxylic acid heptylamide (Example 28, 1.0 g) in tetrahydrofuran (30 mL) under an nitrogen atmosphere cooled to 0° C. was added sodium borohydride (20.7 mmol, 783 mg) in one portion followed by the dropwise addition of boron trifluoride diethyletherate (27.6 mmol, 3.50 ml). The heterogeneous white mixture was allowed to stir at room temperature for 16 hours. The mixture was cooled to 0° C. and 2 M HCl was added until gas evolution ceased, then was heated to 80° C. for 45 minutes. The mixture was cooled to room temperature and concentrated under reduced pressure to a white solid. The solid was suspended in water (50 mL), then treated with 2 M NaOH in order to bring the pH to 14. The basic solution was extracted with diethyl ether (3×). The organic layers were washed with brine (2×), dried over anhydrous sodium sulfate, and concentrated to give impure [4-(1-heptylaminomethyl-cyclopropyl)-phenyl]-methanol as a clear oil. The crude oil was used in the preparation of heptyl-[1-(4-hydroxymethyl-phenyl)-cyclopropylmethyl]-carbamic acid tert-butyl ester without further purification.

Provenance & Evidence