1-Dodecanethiol → 2-(1-(3-Hydroxyphenyl)cyclohexyl)acetic acid

Participants

Reaction Conditions

Reaction Steps

5-(1-(3-Methoxyphenyl)cyclohexyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (105.B) (985 mg, 2.96 mmol) was dissolved in N-methylpyrrolidinone (6.0 mL) and water (53.4 μL, 2.96 mmol) was added. The solution was heated at 120° C. for three hours and LCMS indicated conversion to the anisole carboxylic acid intermediate. The reaction was cooled and NaOH (530 mg, 13.3 mmol) and commercially available dodecane-1-thiol (2.47 mL, 10.4 mmol) were added and the mixture was reheated to 120° C. and stirred for 2.5 days. The reaction was cooled and then diluted with water (75 mL). The mixture was extracted with ether (2×75 mL). The aqueous layer was then acidified with hydrochloric acid and extracted with EtOAc (3×75 mL). The combined EtOAc layers were washed with water (2×100 mL) and brine (1×75 mL) and dried over magnesium sulfate. The filtrate was concentrated to give 2-(1-(3-hydroxyphenyl)cyclohexyl)acetic acid 105.C (1.01 g, 145% yield) with acceptable purity (contains residual N-methylpyrrolidone) to take to the next reaction. MS ESI (neg.) m/e: 233.1 (M−H)−.

Provenance & Evidence