Ammonium Chloride → Cholest-5-ene-1alpha,3beta-diol

HRID 2049946Notes

Reaction equation

HRID 2049946 reaction equation
[O:1]1[C@H:3]2[C:4](=[O:29])[CH:5]=[C:6]3[C@:26]([CH3:27])([C@@H:2]12)[C@@H:25]1[C@H:9]([C@H:10]2[C@:22]([CH3:28])([CH2:23][CH2:24]1)[C@@H:13]([C@H:14]([CH3:21])[CH2:15][CH2:16][CH2:17][CH:18]([CH3:20])[CH3:19])[CH2:12][CH2:11]2)[CH:8]=[CH:7]3.[Cl-].[NH4+]>[Li].N>[OH:1][C@@H:2]1[C@@:26]2([CH3:27])[C:6](=[CH:7][CH2:8][C@@H:9]3[C@@H:25]2[CH2:24][CH2:23][C@@:22]2([CH3:28])[C@H:10]3[CH2:11][CH2:12][C@@H:13]2[C@H:14]([CH3:21])[CH2:15][CH2:16][CH2:17][CH:18]([CH3:20])[CH3:19])[CH2:5][C@@H:4]([OH:29])[CH2:3]1

Participants

4

Reactant 2

HCID 25517Ammonium Chloride2×HCID 139111081alpha,2alpha-Epoxycholesta-4,6-dien-3-one

Product 1

HCID 11112200Cholest-5-ene-1alpha,3beta-diol

Reagents, catalysts & solvents 1

HCID 57431548Lithium ammoniaSolvent

Procedure

One modification of this procedure consists of reducing 1α,2α-epoxycholesta-4,6-dien-3--one in lithium/ammonia prior to protonation of the reaction intermediate enolate with externally added solid ammonium chloride. Our determination that this externally supplied proton source must be added as rapidly as possible led to the present invention. More exactly, when the solid ammonium chloride was added slowly (40-150 minutes) to the reduction reaction mixture, very little of the desired 1α,3β-dihydroxycholest-5-ene could be isolated. When the proton source was added rapidly (less than one minute), the desired product was isolated in high yield. This procedure proved successful for small-scale reactions (5 g or less), but failed completely when attempted on a scaled-up batch (15 g). It was further determined that the addition of the solid ammonium chloride to the larger-scale reaction resulted in uncontrollable foaming, presumably due to heat generation within the reaction flask. As a result, it was necessary to add the solid ammonium chloride to the reduction mixture was slowly (40 to 55 minutes) than had been determined conducive to the production of high yields of the desired reduction product, 1α ,3β-dihydroxycholest-5-ene.

Workup

  1. additionOur determination that this externally supplied proton source must be added as rapidly
  2. customto the reduction reaction mixture

Sources & evidence

ORD record
ord-1be4b793654a437ebb1ee06f97a0d55f
Source dataset
uspto-grants-1980_04
Patent number
US04199518

Reaction notes

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