Sodium Iodide → tert-Butyl 4-(3-(tert-butylcarbamoyl)-2-fluorobenzyl)piperazine-1-carboxylate

HRID 1878407Notes

Reaction equation

HRID 1878407 reaction equation
[N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Br[CH2:15][C:16]1[C:17]([F:29])=[C:18]([CH:26]=[CH:27][CH:28]=1)[C:19]([NH:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].[I-].[Na+].C(N(CC)CC)C>C(#N)C.O.C(OCC)(=O)C>[C:22]([NH:21][C:19]([C:18]1[C:17]([F:29])=[C:16]([CH:28]=[CH:27][CH:26]=1)[CH2:15][N:4]1[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]1)=[O:20])([CH3:25])([CH3:23])[CH3:24]

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 668791623-(bromomethyl)-N-tert-butyl-2-fluorobenzamide

Product 1

HCID 57917710tert-Butyl 4-(3-(tert-butylcarbamoyl)-2-fluorobenzyl)piperazine-1-carboxylateYield 79.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred mixture of tert-butyl piperazine-1-carboxylate (3.53 mmol, 658 mg) in acetonitrile (30 mL) was added 3-(bromomethyl)-N-tert-butyl-2-fluorobenzamide (3.21 mmol, 925 mg), sodium iodide (0.321 mmol, 48.1 mg) and triethylamine (4.82 mmol, 0.671 ml, 487 mg). The reaction mixture was stirred at reflux for 4 hours and then was diluted with water and ethyl acetate. The organic layer was separated, dried and concentrated under reduced pressure. Purification by silica chromatography (eluting with 5% methanol/dichloromethane) gave the title compound (1 g). MS (ESI) m/z 394.1 [M+H]+

Workup

  1. temperatureat reflux for 4 hours
  2. customThe organic layer was separated
  3. customdried
  4. concentrationconcentrated under reduced pressure
  5. customPurification
  6. washby silica chromatography (eluting with 5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-7e2473b96bdb4a12b03005932f728599
Source dataset
uspto-grants-2012_11
Patent number
US08314091B2

Reaction notes

Loading…