Lithium → Cholan-24-oic acid, 3-oxo-, methyl ester, (5alpha)-

HRID 1604619Notes

Reaction equation

HRID 1604619 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](=[CH:16][C:17](=[O:27])[CH2:18][CH2:19]2)[CH2:14][CH2:13]3)[CH2:10][CH2:9]1)[CH3:7].[Li].C(OCC)(=O)C.CCCCCC>CCOCC>[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@H:15]([CH2:16][C:17](=[O:27])[CH2:18][CH2:19]2)[CH2:14][CH2:13]3)[CH2:10][CH2:9]1)[CH3:7]

Participants

5

Reactant 3

HCID 3028194LithiumHCID 110364803-Oxochol-4-en-24-oic acid methyl esterHCID 21226206Ethyl acetate hexane

Product 1

HCID 22821830Cholan-24-oic acid, 3-oxo-, methyl ester, (5alpha)-Yield 41.8%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Into a solution of 3-oxo-4-cholenic acid methyl ester 3002 (13.0 g, 23.68 mmol) in dry ether (50 ml) was added distilled liquid ammonia (70 ml) at -78° C. Lithium (1.0 g, 144.1 mmol) was added in small portions until a blue coloration persisted for 10 minutes, after which the solution was quenched with solid NH4Cl (50 g). Ammonia was evaporated, and the resulting residue was partitioned between water (100 ml) and ether (150 ml). The aqueous solution was extracted further with ether (3×50 ml). The combined extracts were washed with brine (1×70 ml), dried (MgSO4), filtered and concentrated in vacuo to get the crude product. Flash chromatography of the crude product in silica gel using ethyl acetate:hexane (2:8) gave pure 3-oxo-5α-cholanic acid methyl ester 3003 (3.85 g, 29%). 1H NMR (400 MHz, CDCl3 ) δ: 0.69 (3H, s, 18-CH3, 0.91 (3H, d, 21-CH3), 1.02 (3H, s, 19-CH3) and 3.66 (3H, s, CO2CH3).

Workup

  1. distillationdistilled liquid ammonia (70 ml) at -78° C
  2. customafter which the solution was quenched with solid NH4Cl (50 g)
  3. customAmmonia was evaporated
  4. customthe resulting residue was partitioned between water (100 ml) and ether (150 ml)
  5. extractionThe aqueous solution was extracted further with ether (3×50 ml)
  6. washThe combined extracts were washed with brine (1×70 ml)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto get the crude product

Sources & evidence

ORD record
ord-7a11b74d4d1c464fad3adbebc6be62fb
Source dataset
uspto-grants-1999_11
Patent number
US05994336

Reaction notes

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