17-Hydroxyprogesterone → Hydroxyprogesterone Impurity 14

HRID 2059164Notes

Reaction equation

HRID 2059164 reaction equation
[C:1]([O-])(=O)C.[Na+].P(Cl)(Cl)(Cl)=O.[CH3:11][C:12]([C@:14]1([OH:34])[C@@:18]2([CH3:33])[CH2:19][CH2:20][C@@H:21]3[C@:31]4([CH3:32])[C:25](=[CH:26][C:27]([CH2:29][CH2:30]4)=[O:28])[CH2:24][CH2:23][C@H:22]3[C@@H:17]2[CH2:16][CH2:15]1)=[O:13]>C(Cl)(Cl)Cl.C(OCOCC)C>[OH:34][C@:14]1([C@:18]2([CH3:33])[C@H:17]([C@H:22]3[C@H:21]([CH2:20][CH2:19]2)[C@:31]2([CH3:32])[C:25](=[CH:26][C:27](=[O:28])[CH2:29][CH2:30]2)[C:24](=[CH2:1])[CH2:23]3)[CH2:16][CH2:15]1)[C:12](=[O:13])[CH3:11]

Participants

6

Reactant 3

HCID 623817-HydroxyprogesteroneHCID 24813Phosphorus oxychlorideHCID 517045Sodium Acetate

Product 1

HCID 11067843Hydroxyprogesterone Impurity 14Yield 81.2%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 10024DiethoxymethaneSolvent

Conditions

Temperature
65 °C

Procedure

A suspension of 1.0 g of sodium acetate in 30 ml of chloroform, 30 ml of formaldehyde diethylacetal, and 3.8 ml of phosphorus oxychloride is agitated in a two-necked flask for 1 hour at a bath temperature of 65° C. and then combined with 1.0 g of 17α-hydroxyprogesterone. The mixture is stirred for 1.5 hours at 65° C., cooled to room temperature, and under vigorous agitation a saturated soda solution is added dropwise until alkaline reaction occurs. The organic phase is separated, washed neutral with water, dried over sodium sulfate, and concentrated under vacuum. The crude product is purified on 220 g of silica gel with a methylene chloride/acetone gradient (0-12% acetone), thus obtaining 842 mg of 17α-hydroxy-6-methylene-4-pregnene-3,20-dione, mp 218°-220° C.

Workup

  1. stirringThe mixture is stirred for 1.5 hours at 65° C.
  2. temperaturecooled to room temperature
  3. additionunder vigorous agitation a saturated soda solution is added dropwise until alkaline reaction
  4. customThe organic phase is separated
  5. washwashed neutral with water
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customThe crude product is purified on 220 g of silica gel with a methylene chloride/acetone gradient (0-12% acetone)

Sources & evidence

ORD record
ord-9356e66c12e44ed9ae857b5fded72a1e
Source dataset
uspto-grants-1982_03
Patent number
US04322349

Reaction notes

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