1,1'-Carbonyldiimidazole → 4-[4-(4-Bromo-3-trifluoromethoxy-phenylcarbamoyl)-piperazin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1500521Notes

Reaction equation

HRID 1500521 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[O:9][C:10]([F:13])([F:12])[F:11].C1N=CN([C:19](N2C=NC=C2)=[O:20])C=1.[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([N:39]2[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]2)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27]>C(Cl)Cl>[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([N:39]2[CH2:44][CH2:43][N:42]([C:19](=[O:20])[NH:8][C:5]3[CH:6]=[CH:7][C:2]([Br:1])=[C:3]([O:9][C:10]([F:12])([F:11])[F:13])[CH:4]=3)[CH2:41][CH2:40]2)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:27])[CH3:28]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 141291984-Bromo-3-(trifluoromethoxy)anilineHCID 17750358tert-Butyl 4-(piperazin-1-yl)piperidine-1-carboxylate

Product 1

HCID 867005114-[4-(4-Bromo-3-trifluoromethoxy-phenylcarbamoyl)-piperazin-1-yl]-piperidine-1-carboxylic acid tert-butyl esterYield 70.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-bromo-3-trifluoromethoxy-phenylamine (500 mg, 2 mmol) in DCM (5 mL) was added N,N-carbonyldiimidazole (348 mg, 2.15 mmol). The reaction mixture was stirred at RT overnight and then 4-piperazin-1-yl-piperidine-1-carboxylic acid tert-butyl ester (579 mg, 2.15 mmol, Preparation 12) was added and the reaction mixture was stirred at RT for 15 min, and concentrated by rotary evaporation and purified by silica gel chromatography (80 g silica, 0-10% MeOH/DCM) to provide the title intermediate (776 mg, 70% yield) as a yellow powder. (m/z): [M+H]+ calcd for C22H30BrF3N4O4 551.14, found 551.3.

Workup

  1. stirringthe reaction mixture was stirred at RT for 15 min
  2. concentrationconcentrated by rotary evaporation
  3. custompurified by silica gel chromatography (80 g silica, 0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-c7ebaa574e6b4571b73cbee04e231b47
Source dataset
uspto-grants-2015_12
Patent number
US09206159B2

Reaction notes

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