18-Hydroxyandrost-4-ene-3,17-dione → 6beta-Hydroxyandrostenedione

HRID 579718Notes

Reaction equation

HRID 579718 reaction equation
OC[C@]12CC[C@H]3[C@@H](CCC4[C@]3(C)CCC(=O)C=4)[C@@H]1CCC2=O.[OH:23][C@@H:24]1[C:41]2[C@:36]([CH3:43])([CH2:37][CH2:38][C:39](=[O:42])[CH:40]=2)[C@@H:35]2[C@H:26]([C@H:27]3[C@@:31]([CH2:33][CH2:34]2)([CH3:32])[C:30](=[O:44])[CH2:29][CH2:28]3)[CH2:25]1>CCCCCC.C(OCC)(=O)C>[OH:23][C@H:24]1[C:41]2[C@:36]([CH3:43])([CH2:37][CH2:38][C:39](=[O:42])[CH:40]=2)[C@@H:35]2[C@H:26]([C@H:27]3[C@@:31]([CH2:33][CH2:34]2)([CH3:32])[C:30](=[O:44])[CH2:29][CH2:28]3)[CH2:25]1

Participants

4

Reactant 2

HCID 15144818-Hydroxyandrost-4-ene-3,17-dioneHCID 13833941(6alpha)-6-Hydroxyandrost-4-ene-3,17-dione

Product 1

HCID 655446beta-Hydroxyandrostenedione

Reagents, catalysts & solvents 1

HCID 21226206Ethyl acetate hexaneSolvent

Procedure

Meta-chloroperbenzoic acid (11-25 g) was added to the crude 3-acetoxyandrosta-3,5-dien-17-one (i.e., from 15 g of androst-4-ene-3,17-dione) in dioxan (500 ml) and water (5 ml) and cooled to 5° C. in an ice bath. The reaction mixture was then kept at this temperature for 24 h and then diluted with water (500 ml) and extracted with ethyl acetate (3×500 ml). The organic phase was washed with sodium bisulphite (200 ml, 10%), after which a negative starch iodide test was obtained. The organic phase was then washed with a saturated solution of sodium bicarbonate (3×100 ml), a saturated solution of sodium chloride (1×100 ml) dried with sodium sulphate and evaporated to yield a solid (21.7 g). TLC (hexane-ethyl acetate, 1:3) showed no starting material and largely 6β and 6α forms of hydroxyandrost-4-ene-3,17-dione. NMR showed 6β and 6α-hydroxyandrost-4-ene-3,17-dione in a ratio of approximately 4:1. Crystallization of 16.4 g of the crude product from ethyl acetate-hexane (1:3) gave 7.75 g of 6α+6β-hydroxyandrost-4-ene-3,17-dione (with a similar 6α:6β ratio as for crude). The 6α and 6β isomers can be optionally separated if desired although both isomers alone or in admixture can be used. Recrystallization from ethyl acetate gave pure 6β-hydroxyandrost-4-ene-3,17-dione (2.4 g). And, a second crop of crystals contained the 6β and 6α isomers.

Workup

  1. customCrystallization of 16.4 g of the crude product from ethyl acetate-hexane (1:3)

Sources & evidence

ORD record
ord-717480cc9311428bb743147f569f5ad0
Source dataset
uspto-grants-1988_06
Patent number
US04749567

Reaction notes

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