Phenyl isocyanate → 1-(4-benzylbenzyl)-4-[[N-(3-(trifluoromethyl)benzoyl)glycyl]aminomethyl]piperidine

HRID 279316Notes

Reaction equation

HRID 279316 reaction equation
CS(Cl)(=O)=O.C1CCNCC1.[CH2:12]([C:19]1[CH:26]=[CH:25][C:22]([CH2:23]O)=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[F:27][C:28]([F:50])([F:49])[C:29]1[CH:30]=[C:31]([CH:46]=[CH:47][CH:48]=1)[C:32]([NH:34][CH2:35][C:36]([NH:38][CH2:39][CH:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1)=[O:37])=[O:33].C1(N=C=O)C=CC=CC=1>C(Cl)(Cl)Cl.CC#N>[CH2:12]([C:19]1[CH:26]=[CH:25][C:22]([CH2:23][N:43]2[CH2:44][CH2:45][CH:40]([CH2:39][NH:38][C:36](=[O:37])[CH2:35][NH:34][C:32](=[O:33])[C:31]3[CH:46]=[CH:47][CH:48]=[C:29]([C:28]([F:50])([F:49])[F:27])[CH:30]=3)[CH2:41][CH2:42]2)=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

8

Reactant 5

HCID 7672Phenyl isocyanateHCID 8082PiperidineHCID 31297Methanesulfonyl chlorideHCID 5976144-(Phenylmethyl)benzenemethanolHCID 184261644-[{N-(3(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine

Product 1

HCID 184262461-(4-benzylbenzyl)-4-[[N-(3-(trifluoromethyl)benzoyl)glycyl]aminomethyl]piperidine

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

A solution of methanesulfonyl chloride (4.2 mg, 0.037 mmol) in CHCl3 (1.0 mL) and (piperidinomethyl)polystyrene (54 mg, 2.7 mmol base/g resin) were added to a solution of 4-(benzyl)benzyl alcohol (8.7 mg, 0.044 mmol) in CHCl3 (1.0 mL). The reaction mixture was stirred at 25° C. for 15 h. A solution of 4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine (15.1 mg, 0.044 mmol) in CH3CN (1.0 mL) and KI (2 mg) were added to the reaction mixture and the mixture was stirred at 65° C. for 5 h. Phenyl isocyanate (5.2 mg) 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-benzylbenzyl)-4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine (compound No. 926) as a pale yellow oil (5.6 mg, 29): The purity was determined by RPLC/MS (94%); ESI/MS m/e 524.1 (M++H, C30H32F3N3O2).

Workup

  1. stirringthe mixture was stirred at 65° C. for 5 h
  2. stirringthe mixture was stirred at 25° C. for 1 h
  3. washwashed with CH3OH (20 mL)
  4. washProduct was eluted off
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-63dea951cf9e4aa58944cc5c54e33ec2
Source dataset
uspto-grants-2002_03
Patent number
US06362177B1

Reaction notes

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