Water → (2beta,3alpha,5alpha,17beta)-3-Hydroxy-2-(2,2-dimethyl-4-morpholinyl)androstane-17-carbonitrile

HRID 233525Notes

Reaction equation

HRID 233525 reaction equation
Cl.[CH3:2][C:3]1([CH3:9])[O:8][CH2:7][CH2:6][NH:5][CH2:4]1.[OH-].[Na+].[O:12]1[C@H:14]2[CH2:15][C@H:16]3[C@:29]([CH3:31])([CH2:30][C@@H:13]12)[C@@H:28]1[C@H:19]([C@H:20]2[C@@:24]([CH2:26][CH2:27]1)([CH3:25])[C@@H:23]([C:32]#[N:33])[CH2:22][CH2:21]2)[CH2:18][CH2:17]3.O>C(O)CO>[OH:12][C@@H:14]1[C@@H:13]([N:5]2[CH2:6][CH2:7][O:8][C:3]([CH3:9])([CH3:2])[CH2:4]2)[CH2:30][C@@:29]2([CH3:31])[C@@H:16]([CH2:17][CH2:18][C@@H:19]3[C@@H:28]2[CH2:27][CH2:26][C@@:24]2([CH3:25])[C@H:20]3[CH2:21][CH2:22][C@@H:23]2[C:32]#[N:33])[CH2:15]1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 220368882,2-Dimethylmorpholine hydrochlorideHCID 86750183(2alpha,3alpha,5alpha,17beta)-2,3-Epoxyandrostane-17-carbonitrile

Product 1

HCID 54130454(2beta,3alpha,5alpha,17beta)-3-Hydroxy-2-(2,2-dimethyl-4-morpholinyl)androstane-17-carbonitrileYield 54.3%

Reagents, catalysts & solvents 1

HCID 174Ethylene GlycolSolvent

Conditions

Temperature
135 °C

Procedure

2,2-Dimethylmorpholine hydrochloride (2.43 g) and sodium hydroxide (640 mg) were added to a mixture of (2α,3α,5α,17β)-2,3-epoxyandrostane-17-carbonitrile (1.2 g) (prepared as described in British patent 1,434,919) in 1,2-ethanediol (12 ml) and the mixture was heated at 135° C. in an atmosphere of nitrogen for 24 h. The reaction mixture was poured into water (100 ml) and the precipitated solid was filtered off and then dissolved in dichloromethane. The solution was washed with water and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue (1.55 g) was chromatographed on silica gel. The purified product (1.18 g) was crystallised from ether-heptane to give (2β,3α,5α,17β)-3-hydroxy-2-(2,2-dimethyl-4-morpholinyl)androstane-17-carbonitrile (903 mg). m.p. 170°-173° C.; [α]D +117.5° (c 0.8).

Workup

  1. filtrationthe precipitated solid was filtered off
  2. dissolutiondissolved in dichloromethane
  3. washThe solution was washed with water
  4. dry with materialdried over sodium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customthe residue (1.55 g) was chromatographed on silica gel
  7. customThe purified product (1.18 g) was crystallised from ether-heptane

Sources & evidence

ORD record
ord-1f3f1e68229445159021e9436acee179
Source dataset
uspto-grants-1997_01
Patent number
US05593983

Reaction notes

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