Toluene → 3-Oxochol-4-en-24-oic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of 30β-hydroxy-5-cholenic acid methyl ester 3001 (24.16 g, 57.11 mmol), aluminum tri-t-butoxide (56.27 g, 228.43 mmol) and isopropylmethylketone (50 ml) in dry toluene (150 ml) was stirred and heated to 120° C. (oil bath) for 6 hours. The reaction mixture was then cooled to room temperature diluted with toluene (100 ml) and acidified with 2NHCl (70 ml). The organic layer was separated, and the aqueous layer extracted with toluene (3×50 ml). The combined organic extracts were washed with water (1×50 ml), saturated NaHCO3 (2×50 ml), water (1×50 ml), brine (1×50 m), dried (MgSO4), filtered and evaporated in vacuo to get the crude product. Flash chromatography of the crude product using toluene followed by a gradient of ethyl acetate/hexane (5, 10, 20 and 40%) solvent systems gave a pure white solid, 3-oxo-4-cholenic acid methyl ester 3002 (13.43 g, 60%). 1H NMR (400 MHz, CDCl3) δ: 0.71 (3H, s, 18-CH3) 0.90 (3H, d, 21-CH3), 1.17 (3H, S, l9-CH3), 3.66 (3H, s, CO2CH3) and 5.71 (1H, s, 4-H).

Provenance & Evidence