Sodium Chloride → 20-Isocyano-3,3-ethylenedioxypregna-5,17(20)-dien-9alpha-ol

HRID 1613981Notes

Reaction equation

HRID 1613981 reaction equation
CC(C)([O-])C.[K+].[CH2:7]1[CH2:31][O:30][C:9]2([CH2:26][CH2:25][C@@:24]3([CH3:27])[C:11](=[CH:12][CH2:13][C@@H:14]4[C@:23]3([OH:28])[CH2:22][CH2:21][C@@:19]3([CH3:20])[C@H:15]4[CH2:16][CH2:17][C:18]3=O)[CH2:10]2)[O:8]1.[N+:32]([CH:34](P(=O)(OCC)OCC)[CH3:35])#[C-:33].[Cl-].[Na+]>O1CCCC1.O>[N+:32]([C:34](=[C:18]1[C@:19]2([CH3:20])[C@H:15]([C@H:14]3[C@:23]([OH:28])([CH2:22][CH2:21]2)[C@:24]2([CH3:27])[C:11]([CH2:10][C:9]4([O:30][CH2:31][CH2:7][O:8]4)[CH2:26][CH2:25]2)=[CH:12][CH2:13]3)[CH2:16][CH2:17]1)[CH3:35])#[C-:33]

Participants

7

Reactant 4

HCID 5234Sodium ChlorideHCID 11745449Diethyl alpha-isocyanoethylphosphonateHCID 151267113,3-Ethylenedioxy-9alpha-hydroxyandrost-5-en-17-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 5698545720-Isocyano-3,3-ethylenedioxypregna-5,17(20)-dien-9alpha-olYield 69.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
3 °C

Procedure

Under a nitrogen atmosphere potassium tert. butoxide (2.80 g) was added to a stirred solution of 3,3-ethylenedioxy-9α-hydroxyandrost-5-en-17-one (3.70 g) in dry tetrahydrofuran (75 ml) at 0° C. After stirring at this temperature for 10 minutes a solution of diethyl α-isocyanoethylphosphonate (8.09 g) in dry tetrahydrofuran (20 ml) was added dropwise over 45 minutes, while keeping the temperature below 3° C. The reaction mixture was stirred at 3° C. for 5 hours. Stirring was continued at room temperature for 40 hours, then the reaction mixture was poured into a mixture of water (300 ml) and saturated sodium chloride solution (225 ml) and extracted twice with diethyl ether. The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The residue was chromatographed (silica gel, toluene/acetone 5/1) to obtain the title compound (2.86 g) as a mixture of 2 diastereomers.

Workup

  1. additionwas added dropwise over 45 minutes
  2. customthe temperature below 3° C
  3. stirringStirring
  4. waitwas continued at room temperature for 40 hours
  5. extractionextracted twice with diethyl ether
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was chromatographed (silica gel, toluene/acetone 5/1)

Sources & evidence

ORD record
ord-be7f22e80440436e9c2a8828c9835fec
Source dataset
uspto-grants-1993_03
Patent number
US05194602

Reaction notes

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