Benzylamine → N-benzyl [(2S)-1-benzylpiperidin-2-ylmethyl]amine

HRID 1006330Notes

Reaction equation

HRID 1006330 reaction equation
C(Cl)(=O)C(Cl)=O.C(=O)=O.CC(C)=O.[CH2:14]([N:21]1[CH2:26][CH2:25][CH2:24][CH2:23][C@H:22]1[CH2:27]O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[CH2:29]([NH2:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>ClCCl.ClCCCl.O.C(N(CC)CC)C.CS(C)=O>[CH2:29]([NH:36][CH2:27][C@@H:22]1[CH2:23][CH2:24][CH2:25][CH2:26][N:21]1[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

12

Reactant 6

HCID 7504BenzylamineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 7021240(S)-(1-benzylpiperidin-2-yl)methanolHCID 18522661Acetone cardice

Product 1

HCID 69819710N-benzyl [(2S)-1-benzylpiperidin-2-ylmethyl]amine

Reagents, catalysts & solvents 5

HCID 111,2-DichloroethaneSolventHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent3×HCID 8471TriethylamineSolvent

Procedure

A solution of dimethyl sulfoxide (0.219 ml) in dichloromethane (1.1 ml) was added dropwise to a solution of oxalyl chloride (0.133 ml) in dichloromethane (2.7 ml) under cooling below −60° C. with dry ice-acetone. After 5 minutes, the mixture was allowed to −10° C., and a solution of (2S)-1-benzyl-2-(hydroxymethyl)piperidine (156.5 mg) in dichloromethane (1.6 ml) was added to the mixture. The whole mixture was then cooled below −60° C. and was stirred for 20 minutes at the same temperature. After addition of triethylamine (0.64 ml) followed by stirring at room temperature, the reaction mixture was poured into water and extracted with 1,2-dichloroethane. The extract was dried over magnesium sulfate and evaporated under reduced pressure to give a syrup. Benzylamine (0.33 ml) was added to the solution of the syrup obtained above procedure in 1,2-dichloroethane (2.5 ml) with ice-cooling. After the whole was stirred for 30 minutes at the same temperature, sodium triacetoxyborohydride (0.323 g) was added to this mixture. The reaction mixture was allowed to room temperature and was stirred for 3 hours. The mixture was poured into aqueous saturated sodium hydrogen carbonate solution and extracted with dichloromethane. The extract was dried over magnesium sulfate and evaporated under reduced pressure. The resulting residue was purified by silica gel chromatography using a mixture of dichloromethane and methanol (20:1) as an eluent to give N-benzyl-[(2S)-1-benzylpiperidin-2-ylmethyl]amine (168.5 mg).

Workup

  1. customwas allowed to −10° C.
  2. temperatureThe whole mixture was then cooled below −60° C.
  3. stirringby stirring at room temperature
  4. extractionextracted with 1,2-dichloroethane
  5. dry with materialThe extract was dried over magnesium sulfate
  6. customevaporated under reduced pressure
  7. customto give a syrup
  8. temperaturecooling
  9. additionwas added to this mixture
  10. customwas allowed to room temperature
  11. stirringwas stirred for 3 hours
  12. extractionextracted with dichloromethane
  13. dry with materialThe extract was dried over magnesium sulfate
  14. customevaporated under reduced pressure
  15. customThe resulting residue was purified by silica gel chromatography
  16. additiona mixture of dichloromethane and methanol (20:1) as an eluent

Sources & evidence

ORD record
ord-ac28a86fe3484b7c86b5e61478ff6834
Source dataset
uspto-grants-2004_09
Patent number
US06787543B2

Reaction notes

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