Chloroform → 17alpha-Acetoxy-1alpha-chloromethyl-6-methylene-4-pregnene-3,20-dione

HRID 652272Notes

Reaction equation

HRID 652272 reaction equation
[C:1]([O-])(=O)C.[Na+].P(Cl)(Cl)(Cl)=O.[C:11]([O:14][C@:15]1([C@:35]2([CH3:36])[C@H:21]([C@H:22]3[C@H:32]([CH2:33][CH2:34]2)[C@:30]2([CH3:31])[C:25](=[CH:26][C:27](=[O:38])[C@@H:28]4C[C@@H:29]42)[CH2:24][CH2:23]3)[CH2:20][CH2:19]1)[C:16](=[O:18])[CH3:17])(=[O:13])[CH3:12].C(=O)([O-])[O-].[Na+].[Na+].[CH:45]([Cl:48])(Cl)Cl>COCOC.C(Cl)Cl>[C:11]([O:14][C@:15]1([C@:35]2([CH3:36])[C@H:21]([C@H:22]3[C@H:32]([CH2:33][CH2:34]2)[C@:30]2([CH3:31])[C:25](=[CH:26][C:27](=[O:38])[CH2:28][C@@H:29]2[CH2:45][Cl:48])[C:24](=[CH2:1])[CH2:23]3)[CH2:20][CH2:19]1)[C:16](=[O:18])[CH3:17])(=[O:13])[CH3:12]

Participants

8

Reactant 5

HCID 6212ChloroformHCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 517045Sodium AcetateHCID 1351908817alpha-Acetoxy-1alpha,2alpha-methylene-4-pregnene-3,20-dione

Product 1

HCID 1351909017alpha-Acetoxy-1alpha-chloromethyl-6-methylene-4-pregnene-3,20-dione

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8020DimethoxymethaneSolvent

Procedure

A suspension of 9.0 g of sodium acetate in 270 ml of chloroform, 270 ml of formaldehyde dimethylacetal, and 35 ml of phosphorus oxychloride is stirred with 9.0 g of 17α-acetoxy-1α,2α-methylene-4-pregnene-3,20-dione for 5 hours at a bath temperature of 65° C. The reaction solution is neutralized with a saturated sodium carbonate solution and diluted with methylene chloride. The organic phase is separated and worked up as usual. The crude product is purified on 500 g of silica gel with a hexaneethyl acetate gradient (0-30% ethyl acetate), thus isolating 7.5 g of 17α-acetoxy-1α-chloromethyl-6-methylene-4-pregnene-3,20-dione, mp 190°-192° C.

Workup

  1. customThe organic phase is separated
  2. customThe crude product is purified on 500 g of silica gel with a hexaneethyl acetate gradient (0-30% ethyl acetate)

Sources & evidence

ORD record
ord-70a3ff1d95bb4aa79999110f5cd2e578
Source dataset
uspto-grants-1987_06
Patent number
US04670427

Reaction notes

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