Phenylacetic Acid → (1-hydroxycyclohexyl)(phenyl)acetic acid

Participants

Reaction Steps

To a dried 250 mL round bottom flask containing 2 M lithium diisopropyl amide in THF (2 eq.) in THF (329 mL) at 0° C., was added phenyl acetic acid (6 g, 44.07 mmol). The resulting mixture was then stirred at ambient temperature for 30 minutes. The reaction mixture was cooled to −78° C. and cyclohexanone (commercially available from Sigma-Aldrich, Milwaukee, Wis.) (5.49 mL, 52.88 mmol, 1.2 eq.) in THF (181 mL) was added dropwise. The resulting mixture was stirred at −78° C. and allowed to warm to ambient temperature over 3 hours. Reaction progress was monitored by TLC (TLC eluent: 30% EtOAc in hexane). The reaction mixture was then poured into a EtOAc/water mixture, and the aqueous layer was extracted with EtOAc. The aqueous layer was then acidified with dilute hydrochloric acid and extracted with DCM. The DCM solution was washed with brine and concentrated. The product (6.5 g) thus obtained was used without any further purification.

Provenance & Evidence