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

HRID 1173753Notes

Reaction equation

HRID 1173753 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

Intermediate (1b) was dissolved in IPAc (approximately 1 g/10 mL) and the solution was mixed with an equal volume of 1N aqueous HCl. The resulting layers were separated and the aqueous layer was extracted with an equal volume of IPAc. The organic layers were combined, dried over sodium sulfate and filtered. The solvent was removed in vacuo to afford (S)-1-benzyl-3-(1-cyano-1,1-diphenylmethyl)pyrrolidine hydrochloride as a light yellow foamy solid. 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 mixture was heated to 50° C. with stirring for 3 hours. The mixture 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 IPAc (100 mL) and 10% aqueous sodium carbonate (50 mL). The resulting layers were separated and the aqueous layer was extracted with IPAc (50 mL). The organic layers were combined and dried over sodium sulfate (20 g). The sodium sulfate was filtered off and washed with IPAc (20 mL). The solvent was removed in vacuo to afford 5.75 g of intermediate (1c) as a light yellow oil (99.7% yield, 71% purity by HPLC).

Workup

  1. temperatureThe mixture 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 IPAc (100 mL) and 10% aqueous sodium carbonate (50 mL)
  7. customThe resulting layers were separated
  8. extractionthe aqueous layer was extracted with IPAc (50 mL)
  9. dry with materialdried over sodium sulfate (20 g)
  10. filtrationThe sodium sulfate was filtered off
  11. washwashed with IPAc (20 mL)
  12. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-8bae8d8d97af41eab14f4d9cc7afd962
Source dataset
uspto-grants-2010_11
Patent number
US07834185B2

Reaction notes

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