Methanesulfonyl chloride → 3beta-Benzoyloxy-14alpha-cyano-4,4-dimethyl-5alpha-cholest-7-ene

HRID 1493666Notes

Reaction equation

HRID 1493666 reaction equation
[C:1]([O:9][C@H:10]1[CH2:34][CH2:33][C@@:32]2([CH3:35])[C@@H:12]([CH2:13][CH:14](O)[C@@H:15]3[C@@H:31]2[CH2:30][CH2:29][C@@:28]2([CH3:36])[C@@:16]3([C:37]#[N:38])[CH2:17][CH2:18][C@@H:19]2[C@H:20]([CH3:27])[CH2:21][CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[C:11]1([CH3:41])[CH3:40])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CS(Cl)(=O)=O>N1C=CC=CC=1>[C:1]([O:9][C@H:10]1[CH2:34][CH2:33][C@@:32]2([CH3:35])[C@@H:12]([CH2:13][CH:14]=[C:15]3[C@@H:31]2[CH2:30][CH2:29][C@@:28]2([CH3:36])[C@@:16]3([C:37]#[N:38])[CH2:17][CH2:18][C@@H:19]2[C@H:20]([CH3:27])[CH2:21][CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[C:11]1([CH3:41])[CH3:40])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 679240793beta-Benzoyloxy-14alpha-cyano-4,4-dimethyl-5alpha-cholestan-7-ol

Product 1

HCID 679240873beta-Benzoyloxy-14alpha-cyano-4,4-dimethyl-5alpha-cholest-7-eneYield 48.3%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 3β-benzoyloxy-14α-cyano-4,4-dimethyl-5α-cholestan-7-ol (4.5 g, 8 mmole) in pyridine (100 mL) cooled to 0° C. was added methanesulfonyl chloride (2 mL). The reaction mixture was then stirred at 25° C. for 3 hours, poured into ice water, extracted with 4:1 ether/methylene chloride and washed with water The dried, concentrated mesylate was dissolved in collidine (150 mL) and refluxed for 18 hours under argon. The reaction was partitioned between iced HCl and ether/methylene chloride, and the organic extracts were washed with dilute HCl, water, aqueous sodium bicarbonate solution and brine The 6-ene impurity was removed by dissolving the product in methylene chloride, cooling to -78° C. and passing a stream of ozone through the solution until a faint blue color persists The solution was purged with argon and dimethyl sulfide was added and the solution was concentrated in vacuo. The dried, concentrated product was chromatographed over silica gel with 25/1 to 10/1 hexanes in ethyl acetate to afford 3β-benzoyloxy-14α-cyano-4,4-dimethyl-5α-cholest-7-ene (2.1 g, 48%).

Workup

  1. extractionextracted with 4:1 ether/methylene chloride
  2. washwashed with water The dried, concentrated mesylate
  3. dissolutionwas dissolved in collidine (150 mL)
  4. temperaturerefluxed for 18 hours under argon
  5. customThe reaction was partitioned between iced HCl and ether/methylene chloride
  6. washthe organic extracts were washed with dilute HCl, water, aqueous sodium bicarbonate solution and brine The 6-ene impurity
  7. customwas removed
  8. dissolutionby dissolving the product in methylene chloride
  9. temperaturecooling to -78° C.
  10. customwas purged with argon and dimethyl sulfide
  11. additionwas added
  12. concentrationthe solution was concentrated in vacuo
  13. customThe dried, concentrated product was chromatographed over silica gel with 25/1 to 10/1 hexanes in ethyl acetate

Sources & evidence

ORD record
ord-88f799cd1d4d4bf7837528578e41c00c
Source dataset
uspto-grants-1991_06
Patent number
US05023250

Reaction notes

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