N-methyl-2-pyrrolidone → Spironolactone

HRID 2285439Notes

Reaction equation

HRID 2285439 reaction equation
[CH3:1][C:2]12[CH:12]3[CH2:13][CH2:14][C:15]4([CH3:25])[C:19]5([O:24][C:22](=[O:23])[CH2:21][CH2:20]5)[CH2:18][CH2:17][CH:16]4[CH:11]3[CH:10]=[CH:9][C:8]1=[CH:7][C:5](=[O:6])[CH2:4][CH2:3]2.CN1CCCC1=O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[C:45]([OH:48])(=[S:47])[CH3:46]>O.C(O)(=O)C>[CH3:46][C:45]([S:47][C@H:10]1[C@H:11]2[C@H:16]3[C@:15]([CH3:25])([CH2:14][CH2:13][C@@H:12]2[C@:2]2([CH3:1])[C:8](=[CH:7][C:5]([CH2:4][CH2:3]2)=[O:6])[CH2:9]1)[C@@:19]1([O:24][C:22](=[O:23])[CH2:21][CH2:20]1)[CH2:18][CH2:17]3)=[O:48]

Participants

7

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 31926010,13-Dimethyl-1,8,9,10,11,12,13,14,15,16-decahydrospiro[cyclopenta[a]phenanthrene-17,2'-oxolane]-3,5'(2H)-dioneHCID 521998p-Toluenesulfonic acid monohydrateHCID 178418634HCID 178418634, compound

Product 1

HCID 5833Spironolactone

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5.00 g of 17-hydroxy-3-oxo-17α-pregna-4,6-diene- 21-carboxylic acid γ-lactone (99.5% purity, 14.6 mmole), 15 ml of N-methyl-2-pyrrolidone and 228 mg of p-toluene-sulfonic acid monohydrate was heated to 80° C. in a nitrogen atmosphere. Then 3.0 ml of thioacetic acid was added and the mixture was stirred for 2 hours. At a temperature of 80° C., 5 ml of acetic acid was added followed by dropwise addition of 15 ml of water over 5 minutes. After completion of the dropwise addition, the resulting mixture was gradually cooled to 30° C. over an hour and twenty minutes. During the cooling, the acetylthio derivative was precipitated from the solution. Subsequently a mixture of 16.5 ml of methanol and 15 ml of water was added dropwise over 12 minutes. After completion of the dropwise addition, the mixture was stirred at 30° C. for another hour and filtered. The collected cyrstals were washed twice each with 25 ml of an equal volume mixture of methanol and water, and dried at a reduced pressure at 70° C. Thus, 4.7951 g of dried pure spironolactone was obtained as crystals, m.p. 204.4°-206.3° C.

Workup

  1. additionAfter completion of the dropwise addition
  2. temperaturethe resulting mixture was gradually cooled to 30° C. over an hour and twenty minutes
  3. customDuring the cooling, the acetylthio derivative was precipitated from the solution
  4. additionSubsequently a mixture of 16.5 ml of methanol and 15 ml of water
  5. additionwas added dropwise over 12 minutes
  6. additionAfter completion of the dropwise addition
  7. stirringthe mixture was stirred at 30° C. for another hour
  8. filtrationfiltered
  9. washThe collected cyrstals were washed twice each with 25 ml of an equal volume mixture of methanol and water
  10. customdried at a reduced pressure at 70° C

Sources & evidence

ORD record
ord-a3936b898072444c81ec9c5d22f1ce68
Source dataset
uspto-grants-1982_04
Patent number
US04323500

Reaction notes

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