Water → (2beta,3alpha,5alpha,17beta)-3-Hydroxy-2-(2,2-dimethyl-4-morpholinyl)androstan-11-one-17-carbonitrile

HRID 233526Notes

Reaction equation

HRID 233526 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][C:27]1=[O:32])([CH3:25])[C@@H:23]([C:33]#[N:34])[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[C:27](=[O:32])[CH2:26][C@@:24]2([CH3:25])[C@H:20]3[CH2:21][CH2:22][C@@H:23]2[C:33]#[N:34])[CH2:15]1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 220368882,2-Dimethylmorpholine hydrochlorideHCID 8673313717beta-Cyano-2alpha,3alpha-epoxy-5alpha-androstan-11-one

Product 1

HCID 22868795(2beta,3alpha,5alpha,17beta)-3-Hydroxy-2-(2,2-dimethyl-4-morpholinyl)androstan-11-one-17-carbonitrile

Reagents, catalysts & solvents 1

HCID 174Ethylene GlycolSolvent

Conditions

Temperature
120 °C

Procedure

2,2-Dimethylmorpholine hydrochloride (9.67 g) and sodium hydroxide (2.55 g) were added to a mixture (4:1) of (2α,3α,5α,17β)-2,3-epoxyandrostan-11-one-17-carbonitrile and its 3α,4α-epoxy isomer (5.0 g) (British patent 1,434,919) in 1,2-ethanediol (50 ml) and the mixture was heated in an atmosphere of nitrogen at 120° C. for 19 h and then at 150° C. for 4.5 h. The reaction mixture was poured into water (500 ml) and the precipitated solid was filtered off and dissolved in dichloromethane. After washing the solution with water and drying over sodium sulfate, the solvent was removed under reduced pressure and the residue (6.9 g) was chromatographed on silica gel. The purified product (4.3 g) was sequentially crystallised from ethanol and acetone-diethyl ether to give (2β,3α,5α,17β)-3-hydroxy-2-(2,2-dimethyl-4-morpholinyl)androstan-11-one-17-carbonitrile (2.37 g). m.p. 206°-210° C.; [α]D +122.9° (c 0.8).

Workup

  1. filtrationthe precipitated solid was filtered off
  2. dissolutiondissolved in dichloromethane
  3. washAfter washing the solution with water
  4. dry with materialdrying over sodium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customthe residue (6.9 g) was chromatographed on silica gel
  7. customThe purified product (4.3 g) was sequentially crystallised from ethanol and acetone-diethyl ether

Sources & evidence

ORD record
ord-f4f88aa1985a4d4bba0a7bfa29838480
Source dataset
uspto-grants-1997_01
Patent number
US05593983

Reaction notes

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