Methanol, 1-methoxy-, 1-acetate → Megestrol Acetate

HRID 325279Notes

Reaction equation

HRID 325279 reaction equation
[C:1]([O-])(=O)C.[Na+].C(OCOC)(=O)C.[C:13]([O:16][C@:17]1([C@:37]2([CH3:38])[C@H:23]([C@H:24]3[C@H:34]([CH2:35][CH2:36]2)[C@:32]2([CH3:33])[C:27](=[CH:28][C:29](=[O:39])[CH2:30][CH2:31]2)[CH2:26][CH2:25]3)[CH2:22][CH2:21]1)[C:18](=[O:20])[CH3:19])(=[O:15])[CH3:14]>C(Cl)(Cl)Cl.P(Cl)(Cl)(Cl)=O>[C:13]([O:16][C@:17]1([C@:37]2([CH3:38])[C@H:23]([C@H:24]3[C@H:34]([CH2:35][CH2:36]2)[C@:32]2([CH3:33])[C:27](=[CH:28][C:29](=[O:39])[CH2:30][CH2:31]2)[C:26]([CH3:1])=[CH:25]3)[CH2:22][CH2:21]1)[C:18](=[O:20])[CH3:19])(=[O:15])[CH3:14]

Participants

6

Reactant 3

HCID 78087Methanol, 1-methoxy-, 1-acetateHCID 517045Sodium AcetateHCID 10156152Hydroxyprogesterone acetate

Product 1

HCID 11683Megestrol AcetateYield 61%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
70 °C

Procedure

A suspension of 0.5 g of sodium acetate in 60 ml of anhydrous chloroform and 2 ml of distilled phosphorus oxychloride is refluxed under agitation for 30 minutes at a bath temperature of 70° C. After adding 15 ml of methoxymethyl acetate and 2.0 g of 17α-acetoxy-4-pregnene-3,20-dione, the reaction solution is further stirred for 5 hours at 70° C. Subsequently such an amount of a saturated soda solution is added dropwise at room temperature that the aqueous phase remains alkaline. The organic phase is separated, washed with water, and dried over sodium sulfate. After concentration, the crude product is purified on 100 g of silica gel with a hexane-ethyl acetate gradient (0-50% ethyl acetate), thus isolating 1.26 g of 17α-acetoxy-6-methyl-4,6-pregnadiene-3,20-dione, mp 217°-219° C.

Workup

  1. additionSubsequently such an amount of a saturated soda solution is added dropwise at room temperature that the aqueous phase
  2. customThe organic phase is separated
  3. washwashed with water
  4. dry with materialdried over sodium sulfate
  5. concentrationAfter concentration
  6. customthe crude product is purified on 100 g of silica gel with a hexane-ethyl acetate gradient (0-50% ethyl acetate)

Sources & evidence

ORD record
ord-7e982a77634d4de386ec7e10a5b70a8e
Source dataset
uspto-grants-1984_04
Patent number
US04440684

Reaction notes

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