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

HRID 2113095Notes

Reaction equation

HRID 2113095 reaction equation
Cl.C([N:9]1[CH2:13][CH2:12][C@@H:11]([C:14]([C:27]#[N:28])([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10]1)C1C=CC=CC=1.C([O-])=O.[NH4+].O>CO.[Pd]>[C:27]([C:14]([C@@H:11]1[CH2:12][CH2:13][NH:9][CH2:10]1)([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)#[N:28]

Participants

6

Reactant 3

HCID 962WaterHCID 2723923Ammonium formateHCID 66855790((S)-1-benzylpyrrolidin-3-yl)diphenylacetonitrile hydrochloride

Product 1

HCID 22842833(S)-2,2-diphenyl-2-(pyrrolidin-3-yl)acetonitrileYield 99.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of (S)-1-benzyl-3-(1-cyano-1,1-diphenylmethyl)pyrrolidine hydrochloride (8.55 g, 21.98 mmol) in MeOH (44 mL) was added palladium on carbon (1.71 g) and ammonium formate (6.93 g, 109.9 mmol). The reaction mixture was heated to 50° C. with stirring for 3 hours. The reaction was cooled to ambient temperature and water (20 mL) was added. The resulting mixture was filtered through a pad of Celite, washing with MeOH (20 mL). The filtrate was collected and most of the MeOH was removed in vacuo. The residue was mixed with iPrAc (100 mL) and 10% aqueous sodium carbonate (50 mL). The resulting layers were separated and the aqueous layer was extracted with iPrAc (50 mL). The organic layers were combined and dried over sodium sulfate (20 g). The sodium sulfate was filtered off and washed with iPrAc (20 mL). The solvent was removed in vacuo to afford 5.75 g of the title intermediate as a light yellow oil (99.7% yield, 71% purity by HPLC).

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. filtrationThe resulting mixture was filtered through a pad of Celite
  3. washwashing with MeOH (20 mL)
  4. customThe filtrate was collected and most of the MeOH
  5. customwas removed in vacuo
  6. additionThe residue was mixed with iPrAc (100 mL) and 10% aqueous sodium carbonate (50 mL)
  7. customThe resulting layers were separated
  8. extractionthe aqueous layer was extracted with iPrAc (50 mL)
  9. dry with materialdried over sodium sulfate (20 g)
  10. filtrationThe sodium sulfate was filtered off
  11. washwashed with iPrAc (20 mL)
  12. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-a6fc64d14a9541a8b27d1964712ee3d5
Source dataset
uspto-grants-2009_04
Patent number
US07524880B2

Reaction notes

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