Hydrogen Bromide → (S)-2,2-diphenyl-2-(pyrrolidin-3-yl)acetonitrile

HRID 2371881Notes

Reaction equation

HRID 2371881 reaction equation
[C:1]([C:3]([C@@H:16]1[CH2:20][CH2:19][N:18](S(C2C=CC(C)=CC=2)(=O)=O)[CH2:17]1)([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)#[N:2].Br.C1(O)C=CC=CC=1>ClCCl>[C:1]([C:3]([C@@H:16]1[CH2:20][CH2:19][NH:18][CH2:17]1)([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)#[N:2]

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 996PhenolHCID 22842832[(3S)-1-(4-Methylbenzene-1-sulfonyl)pyrrolidin-3-yl](diphenyl)acetonitrile

Product 1

HCID 22842833(S)-2,2-diphenyl-2-(pyrrolidin-3-yl)acetonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A mixture containing 3-(S)-(+)-(1-cyano-1,1-diphenylmethyl)-1-tosylpyrrolidine (49 g--see Preparation 6(B)), 48% aqueous hydrobromic acid (500 ml) and phenol (50 g) was heated under reflux for 1.25 hours then allowed to cool to room temperature. The mixture was extracted with ether (50 ml) to remove an upper layer of purple oil, then with 2:1 ether/hexane (150 ml). The aqueous layer was extracted with dichloromethane (4×100 ml), the dichloromethane extracts were combined, washed with 10% aqueous sodium hydroxide (3×50 ml), then dried (MgSO4) and concentrated in vacuo to give an oil. The original ether extract was concentrated in vacuo to give an oil which was dissolved in dichloromethane (100 ml) and washed with 10% aqueous sodium hydroxide (3×50 ml). The dichloromethane solution was dried (MgSO4) and concentrated in vacuo to give an oil which was combined with that obtained from the initial dichloromethane extraction. The combined oils were then dissolved in dichloromethane (200 ml) and washed with 10% aqueous sodium hydroxide solution (2×50 ml). The dichloromethane solution was dried (MgSO4) and concentrated in vacuo to give an oil which was purified by column chromatography on silica eluting with dichloromethane containing methanol (0% up to 10%). The product-containing fractions were combined and concentrated in vacuo to give the title compound as a foam, yield, 24.3 g, [α]D25 +6.0° (c 1.0, CH2Cl2).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 1.25 hours
  3. extractionThe mixture was extracted with ether (50 ml)
  4. customto remove an upper layer of purple oil
  5. extractionThe aqueous layer was extracted with dichloromethane (4×100 ml)
  6. washwashed with 10% aqueous sodium hydroxide (3×50 ml)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customto give an oil
  10. extractionThe original ether extract
  11. concentrationwas concentrated in vacuo
  12. customto give an oil which
  13. washwashed with 10% aqueous sodium hydroxide (3×50 ml)
  14. dry with materialThe dichloromethane solution was dried (MgSO4)
  15. concentrationconcentrated in vacuo
  16. customto give an oil which
  17. washwashed with 10% aqueous sodium hydroxide solution (2×50 ml)
  18. dry with materialThe dichloromethane solution was dried (MgSO4)
  19. concentrationconcentrated in vacuo
  20. customto give an oil which
  21. customwas purified by column chromatography on silica eluting with dichloromethane
  22. additioncontaining methanol (0% up to 10%)
  23. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-16a8982a0984461cae2db2d092089842
Source dataset
uspto-grants-1992_03
Patent number
US05096890

Reaction notes

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