Dimethylformamide → (2beta,3alpha,5alpha)-3-Hydroxy-2-(2,2-dimethyl-4-morpholinyl)-11,20-dioxopregnane-21-carbonitrile

HRID 233522Notes

Reaction equation

HRID 233522 reaction equation
Cl[CH2:2][C:3](=[O:33])[C@@H:4]1[C@:21]2([CH3:22])[C@H:7]([C@H:8]3[C@H:18]([C:19](=[O:23])[CH2:20]2)[C@:16]2([CH3:17])[C@H:11]([CH2:12][C@H:13]([OH:32])[C@@H:14]([N:24]4[CH2:29][CH2:28][O:27][C:26]([CH3:31])([CH3:30])[CH2:25]4)[CH2:15]2)[CH2:10][CH2:9]3)[CH2:6][CH2:5]1.[C-]#N.[Na+].[CH3:37][N:38](C)C=O>CO.O>[OH:32][C@@H:13]1[C@@H:14]([N:24]2[CH2:29][CH2:28][O:27][C:26]([CH3:31])([CH3:30])[CH2:25]2)[CH2:15][C@@:16]2([CH3:17])[C@@H:11]([CH2:10][CH2:9][C@@H:8]3[C@@H:18]2[C:19](=[O:23])[CH2:20][C@@:21]2([CH3:22])[C@H:7]3[CH2:6][CH2:5][C@@H:4]2[C:3](=[O:33])[CH2:2][C:37]#[N:38])[CH2:12]1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 8929Sodium CyanideHCID 10672358(2beta,3alpha,5alpha)-21-Chloro-3-hydroxy-2-(2,2-dimethyl-4-morpholinyl)pregnane-11,20-dione

Product 1

HCID 53955604(2beta,3alpha,5alpha)-3-Hydroxy-2-(2,2-dimethyl-4-morpholinyl)-11,20-dioxopregnane-21-carbonitrile

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

A stirred mixture of (2β,3α,5α)-21-chloro-3-hydroxy-2-(2,2-dimethyl-4-morpholinyl)pregnane-11,20-dione (500 mg), sodium cyanide (500 mg), N,N-dimethylformamide (1.25 ml) in methanol (10 ml) and water (0.25 ml) was heated under reflux for 16 h. The resulting solution was cooled and poured into water (50 ml). The mixture was extracted with dichloromethane and the organic layer was washed with water to pH 7. After drying the solution over sodium sulfate, the solvent was removed under reduced pressure and the residue (430 mg) was chromatographed on silica gel. The purified product (208 mg) was crystallised from dichloromethane-methanol to give (2β,3α,5α)-3-hydroxy-2-(2,2-dimethyl-4-morpholinyl)-11,20-dioxopregnane-21-carbonitrile (96 mg). δ (CDCl3) 0.62 (s, 3H), 1.06 (s,3H), 1.22 (s,3H), 1.26 (s,3H) and 3.38 (s,2H).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 16 h
  3. temperatureThe resulting solution was cooled
  4. extractionThe mixture was extracted with dichloromethane
  5. washthe organic layer was washed with water to pH 7
  6. dry with materialAfter drying the solution over sodium sulfate
  7. customthe solvent was removed under reduced pressure
  8. customthe residue (430 mg) was chromatographed on silica gel
  9. customThe purified product (208 mg) was crystallised from dichloromethane-methanol

Sources & evidence

ORD record
ord-0c5dc6cf033d453fb9c7a42212f69715
Source dataset
uspto-grants-1997_01
Patent number
US05593983

Reaction notes

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