Methanol → Diphenyl(pyrrolidin-3-yl)acetonitrile

HRID 1742702Notes

Reaction equation

HRID 1742702 reaction equation
[C:1]([C:3]([CH: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].C1(O)C=CC=CC=1.[OH-].[Na+].CO>Br.O.CCCCCC.C1(C)C=CC=CC=1>[C:1]([C:3]([CH: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

8

Reactant 4

HCID 887MethanolHCID 996PhenolHCID 14798Sodium HydroxideHCID 22340524{1-[(4-Methylphenyl)sulfonyl]-3-pyrrolidinyl}(diphenyl)acetonitrile

Product 1

HCID 13633741Diphenyl(pyrrolidin-3-yl)acetonitrile

Reagents, catalysts & solvents 3

HCID 260Hydrogen BromideSolventHCID 962WaterSolventHCID 21889329Toluene hexaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-(R,S)-(1-cyano-1,1-diphenylmethyl)-1-tosylpyrrolidine (21 g--see Preparation 6(A)) and phenol (21 g) in 48% aqueous hydrobromic acid (240 ml) was heated under reflux for 2 hours. The mixture was cooled to 0° C. in an ice bath and basified (pH 12) by the slow addition of 50% aqueous sodium hydroxide (280 ml). Methanol (10 ml) was added and the mixture was stirred for 15 minutes then diluted with water (300 ml). The mixture was extracted with dichloromethane (3×200 ml), the combined extracts were dried (MgSO4) and concentrated in vacuo to give an oil. The oil was dissolved in 1:1 hexane/toluene (500 ml) and washed with 0.5 M hydrochloric acid (3×500 ml). The aqueous extracts, together with some oil which separated during the extraction, were basified (pit 12) by the addition of aqueous sodium hydroxide (12 g in 20 ml water) and the mixture was extracted with dichloromethane (3×150 ml). The combined dichloromethane extracts were 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 oil, yield 10 g.

Workup

  1. temperatureunder reflux for 2 hours
  2. extractionThe mixture was extracted with dichloromethane (3×200 ml)
  3. dry with materialthe combined extracts were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customto give an oil
  6. washwashed with 0.5 M hydrochloric acid (3×500 ml)
  7. customThe aqueous extracts, together with some oil which separated during the extraction
  8. additionby the addition of aqueous sodium hydroxide (12 g in 20 ml water)
  9. extractionthe mixture was extracted with dichloromethane (3×150 ml)
  10. dry with materialThe combined dichloromethane extracts were dried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. customto give an oil which
  13. customwas purified by column chromatography on silica eluting with dichloromethane
  14. additioncontaining methanol (0% up to 10%)
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8ea3ae0724c04cc38422fa866637f7b7
Source dataset
uspto-grants-1994_08
Patent number
US05340831

Reaction notes

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