3-Methyl-2-butanone → 3-Oxochol-4-en-24-oic acid methyl ester

Temperature

120 °C

A solution of 3β-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 40t) 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 (3 H, s, 18-CH3), 0.90 (3 H, d, 21-CH3), 1.17 (3 H, S, 19-CH3), 3.66 (3 H, s, CO2CH3 and 5.71 (1 H, s, 4-H).

1. temperatureThe reaction mixture was then cooled to room temperature
2. customThe organic layer was separated
3. extractionthe aqueous layer extracted with toluene (3×50 ml)
4. washThe combined organic extracts were washed with water (1×50 ml), saturated NaHCO3 (2×50 ml), water (1×50 ml), brine (1×50 m)
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. customevaporated in vacuo
8. customto get the crude product

ORD record

ord-31197c4d0e5b44b28ea796f58bfbf8e5

Source dataset

uspto-grants-1998_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05840740