Phenylacetaldehyde → 1-(2-Phenylethyl)-3-(SR)-((4-phenyl)piperidin-1-yl)methyl-4-(SR)-phenylpyrrolidine

HRID 1276503Notes

Reaction equation

HRID 1276503 reaction equation
[C:1]1([CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][CH:14]3[CH:18]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH2:17][NH:16][CH2:15]3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:25]1([CH2:31][CH:32]=O)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([BH3-])#N.[Na+]>CO.CC(O)=O>[C:25]1([CH2:31][CH2:32][N:16]2[CH2:17][CH:18]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:14]([CH2:13][N:10]3[CH2:9][CH2:8][CH:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH2:12][CH2:11]3)[CH2:15]2)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

6

Reactant 3

HCID 998PhenylacetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 545487023-(RS)-((4-phenyl)piperidin-1-yl)methyl-4-(SR)-phenylpyrrolidine

Product 1

HCID 538707701-(2-Phenylethyl)-3-(SR)-((4-phenyl)piperidin-1-yl)methyl-4-(SR)-phenylpyrrolidineYield 48%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent

Procedure

A mixture of 50 mg (0.16 mmol) 3-(SR)-((4-phenyl)piperidin-1-yl)methyl-4-(SR)-phenylpyrrolidine (from Example 30, Step A) and 37 mg (0.31 mmol) of phenylacetaldehyde and 100 mg 4 A powdered molecular sieves in 3 mL of MeOH was treated with 18 mg (0.28 mmol) of sodium cyanoborohydride and 2 drops of HOAc and stirred at rt for 18 h. The mixture was filtered onto a pad of Celite; the pad and flask were rinsed well with MeOH (25 mL). The filtrate was concentrated in vacuo and the residue was partitioned between 25 mL of EtOAc and 15 mL of sat'd NaHCO3 and the layers were separated. The organic layer was dried over MgSO4 and concentrated in vacuo. Flash chromatography on 15 g of silica gel using 2:1 v/v hexanes/EtOAc afforded 32 mg (48%) of the title compound as an oil. 1H NMR (500 MHz, CDCl3): δ1.66-2.04 (6H), 2.42-3.13 (15H), 7.20-7.37 (15H). Mass Spectrum (NH3 -CI): 427 (M+1).

Workup

  1. filtrationThe mixture was filtered onto a pad of Celite
  2. washthe pad and flask were rinsed well with MeOH (25 mL)
  3. concentrationThe filtrate was concentrated in vacuo
  4. customthe residue was partitioned between 25 mL of EtOAc and 15 mL of sat'd NaHCO3
  5. customthe layers were separated
  6. dry with materialThe organic layer was dried over MgSO4
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-02d8fd0156d44ebbb6b8fa0a8b9c38da
Source dataset
uspto-grants-2000_12
Patent number
US06166037

Reaction notes

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