1-(Bromomethyl)-4-(trifluoromethoxy)benzene → cis-2-[(4-Chlorobenzenesulfonyl)-(4-trifluoromethoxy-benzyl)-amino]-cyclohexanecarboxylic acid amide

HRID 7036

Reaction equation

HRID 7036 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C@H:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@H:13]2[C:18]([NH2:20])=[O:19])(=[O:10])=[O:9])=[CH:4][CH:3]=1.Br[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[CH:25][CH:24]=1>C(#N)C.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][C:30]([F:31])([F:32])[F:33])=[CH:25][CH:24]=2)[C@H:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@H:13]2[C:18]([NH2:20])=[O:19])(=[O:9])=[O:10])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 1427851-(Bromomethyl)-4-(trifluoromethoxy)benzeneHCID 69655699cis-2-(4-Chlorobenzenesulfonylamino)-cyclohexanecarboxylic acid amide

Product 1

HCID 69655582cis-2-[(4-Chlorobenzenesulfonyl)-(4-trifluoromethoxy-benzyl)-amino]-cyclohexanecarboxylic acid amideYield 67%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

cis-2-(4-Chloro-benzenesulfonylamino)-cyclohexanecarboxylic acid amide (200 mg, 0.63 mmol), CsCO3 (250 mg, 0.76 mmol), and 1-bromomethyl-4-trifluoromethoxy-benzene (155 mg, 0.69 mmol) was stirred in acetonitrile (15 mL) at room temperature for 18 h. The reaction was then diluted with EtOAc (150 mL) and washed with H2O, brine, dried over Na2SO4 and concentrated to give a crude white wax. Further purification by flash chromatography (silica gel, 0.5%–1% MeOH/CHCl3) afforded the titled compound (205 mg) as a white solid in 67% yield: 1H NMR (DMSO-d6) δ 7.75 (d, 2 H, J=8.0 Hz), 7.59 (d, 2 H, J=8.0 Hz), 7.36 (m, 3 H), 7.21 (d, 2 H, J=8.0 Hz), 6.69 (s br, 1 H), 4.58 (AB2, 2 H, Δv=17, Jab=64 Hz), 3.89 (m, 1 H), 2.79 (s, 1 H), 2.44 (m, 1 H), 1.78 (m, 1 H), 1.66 (m, 2 H), 1.31 (m, 3 H), 0.98 (m, 1 H); MS m/e 491.03 (M+H)+.

Workup

  1. washwashed with H2O, brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customto give a crude white wax
  5. customFurther purification by flash chromatography (silica gel, 0.5%–1% MeOH/CHCl3)

Sources & evidence

ORD record
ord-ed10b2c70d2b47c3a62ee8f7be7d71c0
Source dataset
uspto-grants-2006_08
Patent number
US07084178B2

Linked notes

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