Methyl iodide → 1-(4-chlorobenzyl)-1-methyl-4-[[N-[3-(trifluoromethyl)benzoyl]glycyl]aminomethyl]piperidinium iodide

HRID 2187857Notes

Reaction equation

HRID 2187857 reaction equation
[I:1][CH3:2].[Cl:3][C:4]1[CH:34]=[CH:33][C:7]([CH2:8][N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][NH:16][C:17](=[O:32])[CH2:18][NH:19][C:20](=[O:31])[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[CH2:11][CH2:10]2)=[CH:6][CH:5]=1>CC#N>[I-:1].[Cl:3][C:4]1[CH:34]=[CH:33][C:7]([CH2:8][N+:9]2([CH3:2])[CH2:14][CH2:13][CH:12]([CH2:15][NH:16][C:17](=[O:32])[CH2:18][NH:19][C:20](=[O:31])[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:29])([F:30])[F:28])[CH:22]=3)[CH2:11][CH2:10]2)=[CH:6][CH:5]=1

Participants

4

Reactant 2

HCID 6328Methyl iodideHCID 508750N-({[1-(4-Chloro-benzyl)-piperidin-4-ylmethyl]-carbamoyl}-methyl)-3-trifluoromethyl-benzamide

Product 1

HCID 184262121-(4-chlorobenzyl)-1-methyl-4-[[N-[3-(trifluoromethyl)benzoyl]glycyl]aminomethyl]piperidinium iodideYield 71%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine (30 mg, 0.087 mmol) in CH3CN (1.0 mL) and (piperidinomethyl)polystyrene (80 mg, 2.7 mmol base/g resin) were added to a solution of 4-chlorobenzyl chloride (11.7 mg, 0.073 mmol) in CH3CN (1.0 mL). The reaction mixture was stirred at 60° C. for 2 h. Phenyl isocyanate (10.4 mg, 0.087 mmol) was added to the cooled reaction mixture and the mixture was stirred at 25° C. for 1 h. The reaction mixture was loaded onto Varian™ SCX column and washed with CH3OH (20 mL). Product was eluted off using 2 N NH3 in CH3OH (6 mL) and concentrated to afford 1-(4-chlorobenzyl)-4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine as a colorless oil used without purification. Iodomethane (28 mg, 0.20 mmol) was added to a solution of 1-(4-chlorobenzyl)-4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine in CH3CN (2.0 mL) and the reaction mixture was stirred at 70° C. for 4 h. The solvent was removed under reduced pressure to afford 1-(4-chlorobenzyl)-1-methyl-4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidinium iodide as a pale yellow oil (31.7 mg, 71%): The purity was determined by RPLC/MS (99%); ESI/MS m/e 482.1 (M+, C24H28ClF3N3O2).

Workup

  1. customused without purification
  2. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-4e17dd4c533948fa8801573c10feb211
Source dataset
uspto-grants-2002_06
Patent number
US06410566B1

Reaction notes

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