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

Temperature

120 °C

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)−.

1. temperatureThe reaction was cooled
2. customwas reheated to 120° C.
3. temperatureThe reaction was cooled
4. extractionThe mixture was extracted with ether (2×75 mL)
5. extractionextracted with EtOAc (3×75 mL)
6. washThe combined EtOAc layers were washed with water (2×100 mL) and brine (1×75 mL)
7. dry with materialdried over magnesium sulfate
8. concentrationThe filtrate was concentrated

ORD record

ord-f313945ff1d24c94a3fc3ec81928e8b3

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08030354B2