Benzaldehyde → cis-1-Benzyl-3-benzylaminomethyl-4-methylpyrrolidine

HRID 424722Notes

Reaction equation

HRID 424722 reaction equation
[CH2:1]([N:8]1[CH2:12][C@H:11]([CH3:13])[C@H:10]([CH2:14][NH2:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:16](=O)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C([BH3-])#N.[Na+].[OH-].[Na+]>CO>[CH2:1]([N:8]1[CH2:12][C@H:11]([CH3:13])[C@H:10]([CH2:14][NH:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydride2×HCID 15206166cis-1-Benzyl-4-methyl-3-aminomethylpyrrolidine

Product 1

HCID 66704887cis-1-Benzyl-3-benzylaminomethyl-4-methylpyrrolidine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

cis-1-Benzyl-4-methyl-3-aminomethylpyrrolidine (1000 mg) was dissolved in methanol (10 mL). While this solution was chilled in an ice water bath, benzaldehyde (0.50 mL) was added dropwise and the mixture was stirred at room temperature for 1 hour. Subsequently, sodium cyanoborohydride (184 mg) was added and the mixture was stirred at room temperature for 1.5 hours, followed by addition of a second portion of sodium cyanoborohydride (123 mg) and then further stirring for 5.5 hours. To the resulting mixture, a 2 mol/L aqueous solution of sodium hydroxide (5 mL) was added and the mixture was refluxed for 2 hours. Subsequently, the reaction mixture was concentrated under reduced pressure and the residue was extracted with toluene (2×30 mL). The toluene layers were combined, washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to give cis-1-benzyl-3-benzylaminomethyl-4-methylpyrrolidine as a pale yellow oil (690 mg).

Workup

  1. temperatureWhile this solution was chilled in an ice water bath
  2. stirringthe mixture was stirred at room temperature for 1.5 hours
  3. stirringfurther stirring for 5.5 hours
  4. temperaturethe mixture was refluxed for 2 hours
  5. concentrationSubsequently, the reaction mixture was concentrated under reduced pressure
  6. extractionthe residue was extracted with toluene (2×30 mL)
  7. washwashed with water
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-472cdca8b1274dccbc04586bde226a0e
Source dataset
uspto-grants-2012_01
Patent number
US08106072B2

Reaction notes

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