Ammonium formate → 3-(RS)-((4-phenyl)piperidin-1-yl)methyl-4-(SR)-phenylpyrrolidine

HRID 1276500Notes

Reaction equation

HRID 1276500 reaction equation
C1(C[N:8]2[CH2:12][CH:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:10]([CH2:19][N:20]3[CH2:25][CH2:24][CH:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH2:22][CH2:21]3)[CH2:9]2)C=CC=CC=1.C([O-])=O.[NH4+]>CO.[OH-].[OH-].[Pd+2]>[C:26]1([CH:23]2[CH2:22][CH2:21][N:20]([CH2:19][CH:10]3[CH:11]([C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=4)[CH2:12][NH:8][CH2:9]3)[CH2:25][CH2:24]2)[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 221160821-phenylmethyl-3-(SR)-((4-phenyl) piperidin-1-yl)methyl-4-(SR)-phenylpyrrolidine

Product 1

HCID 545487023-(RS)-((4-phenyl)piperidin-1-yl)methyl-4-(SR)-phenylpyrrolidineYield 98.8%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

A mixture of 232 mg (0.6 mmol) of 1-phenylmethyl-3-(SR)-((4-phenyl) piperidin-1-yl)methyl-4-(SR)-phenylpyrrolidine (from Example 9, Step B), 894 mg (14.1 mmol) of ammonium formate and 116 mg of 20% Pd(OH)2 on carbon in 10 mL of MeOH was heated at reflux for 1 h. The reaction mixture was cooled and filtered througha pad of Celite. The reaction flask and filtered solids were rinsed with 50 mL of EtOAc and the filtrate was concentrated in vacuo. The residue was partitioned between 50 mL of EtOAc and 30 mL of sat'd NaHCO3 and the layers were separated. The organic layer was dried over MgSO4. The aqueous layer was extracted with 50 mL of EtOAc; the extract was dried and the organic layers were combined and concentrated in vacuo to afford 190 mg (95%) of the title compound as an oil. 1H NMR (500 MHz, CDCl3): δ1.63-1.80 (m, 4H), 1.93-2.05 (m, 2H), 2.39-2.53 (m, 5H), 2.83 (d, J=10.7, 1H), 2.93-3.02 (m, 2H), 3.08 (t, J=9.6, 1H), 3-47-3.53 (m, 1H ), 5.19 (br s, 1H ), 7.19-7.38 (1OH). Mass Spectrum (NH3 -CI): 321 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 h
  3. temperatureThe reaction mixture was cooled
  4. filtrationfiltered througha pad of Celite
  5. filtrationThe reaction flask and filtered solids
  6. washwere rinsed with 50 mL of EtOAc
  7. concentrationthe filtrate was concentrated in vacuo
  8. customThe residue was partitioned between 50 mL of EtOAc and 30 mL of sat'd NaHCO3
  9. customthe layers were separated
  10. dry with materialThe organic layer was dried over MgSO4
  11. extractionThe aqueous layer was extracted with 50 mL of EtOAc
  12. customthe extract was dried
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0079ccab0f2a4fa8a817768caa0a810d
Source dataset
uspto-grants-2000_12
Patent number
US06166037

Reaction notes

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