Hydrochloric Acid → ((S)-1-benzylpyrrolidin-3-yl)diphenylacetonitrile hydrochloride

HRID 389339Notes

Reaction equation

HRID 389339 reaction equation
[CH2:1]([N:8]1[CH2:12][CH2:11][C@@H:10]([C:13]([C:26]#[N:27])([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:28]>>[ClH:28].[CH2:1]([N:8]1[CH2:12][CH2:11][C@@H:10]([C:13]([C:26]#[N:27])([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 13633739((S)-1-Benzylpyrrolidin-3-yl)diphenylacetonitrile

Product 1

HCID 66855790((S)-1-benzylpyrrolidin-3-yl)diphenylacetonitrile hydrochloride

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. customThe resulting layers were separated
  2. extractionthe aqueous layer was extracted with an equal volume of IPAc
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-f33adad55c35496d8544236ecc5df1f8
Source dataset
uspto-grants-2013_02
Patent number
US08378121B2

Reaction notes

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