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

HRID 482334Notes

Reaction equation

HRID 482334 reaction equation
[CH3:1][O:2][C:3](=[O:28])[CH2:4][CH2:5][C@H:6]([C@@H:8]1[C@:25]2([CH3:26])[C@H:11]([C@H:12]3[C@H:22]([CH2:23][CH2:24]2)[C@:20]2([CH3:21])[C:15]([CH2:16][C@@H:17]([OH:27])[CH2:18][CH2:19]2)=[CH:14][CH2:13]3)[CH2:10][CH2:9]1)[CH3:7].CC(C)([O-])C.CC(C)([O-])C.CC(C)([O-])C.[Al+3].C(C(C)=O)(C)C.C(OCC)(=O)C.CCCCCC>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:28])[CH2:4][CH2:5][C@H:6]([C@@H:8]1[C@:25]2([CH3:26])[C@H:11]([C@H:12]3[C@H:22]([CH2:23][CH2:24]2)[C@:20]2([CH3:21])[C:15](=[CH:16][C:17](=[O:27])[CH2:18][CH2:19]2)[CH2:14][CH2:13]3)[CH2:10][CH2:9]1)[CH3:7]

Participants

6

Reactant 4

HCID 112513-Methyl-2-butanoneHCID 68399Aluminum tert-butoxideHCID 11153463CHOL-5-EN-24-oic acid, 3-hydroxy-, methyl ester, (3beta)-HCID 21226206Ethyl acetate hexane

Product 1

HCID 110364803-Oxochol-4-en-24-oic acid methyl esterYield 60.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Conditions

Temperature
120 °C

Procedure

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 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, 19-CH3), 3.66 (3H, s, CO2CH3) and 5.71 (1H, s, 4-H).

Workup

  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

Sources & evidence

ORD record
ord-e7f09b0ba646417c8ab3c9f3524134e7
Source dataset
uspto-grants-1998_08
Patent number
US05795885

Reaction notes

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