Phenyl isocyanate → 1-{3-(trifluoromethoxy)benzyl}-4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine

HRID 279313Notes

Reaction equation

[F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]([CH:20]=[CH:21][CH:22]=1)[C:6]([NH:8][CH2:9][C:10]([NH:12][CH2:13][CH:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)=[O:11])=[O:7].C1CCNCC1.[F:31][C:32]([F:43])([F:42])[O:33][C:34]1[CH:35]=[C:36]([CH:39]=[CH:40][CH:41]=1)[CH2:37]Br.C1(N=C=O)C=CC=CC=1>CC#N>[F:31][C:32]([F:42])([F:43])[O:33][C:34]1[CH:35]=[C:36]([CH:39]=[CH:40][CH:41]=1)[CH2:37][N:17]1[CH2:18][CH2:19][CH:14]([CH2:13][NH:12][C:10](=[O:11])[CH2:9][NH:8][C:6](=[O:7])[C:5]2[CH:20]=[CH:21][CH:22]=[C:3]([C:2]([F:1])([F:23])[F:24])[CH:4]=2)[CH2:15][CH2:16]1

Participants

Conditions

Temperature: 60 °C

Procedure

A solution of 4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine (19.9 mg, 0.058 mmol) in CH3CN (1.0 mL) and (piperidinomethyl)polystyrene (55 mg, 2.7 mmol base/g resin) were added to a solution of 3-(trifluoromethoxy)benzyl bromide (12.3 mg, 0.048 mmol) in CH3CN (1.0 mL). The reaction mixture was stirred at 60° C. for 2.5 h. Phenyl isocyanate (6.9 mg, 0.048 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-{3-(trifluoromethoxy)benzyl}-4-[{N-(3-(trifluoromethyl)benzoyl)glycyl}aminomethyl]piperidine (compound No. 927) (22.8 mg, 91%) as a pale yellow oil: The purity was determined by RPLC/MS (99%); ESI/MS m/e 518.1 (M++H, C24H25F6N3O3).

Workup

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

Sources & evidence

ORD record: ord-7d7c201906764915a8ed2d31a5dacc89
Source dataset: uspto-grants-2002_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06362177B1

Reaction notes

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