1-Cyclohexenylboronic acid → 4-(1-Cyclohexen-1-yl)-3-(trifluoromethyl)benzamide

HRID 423343Notes

Reaction equation

HRID 423343 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[C:10]([F:13])([F:12])[F:11].[C:14]1(B(O)O)[CH2:19][CH2:18][CH2:17][CH2:16][CH:15]=1.C[O-:24].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CO>[C:14]1([C:2]2[CH:9]=[CH:8][C:5]([C:6]([NH2:7])=[O:24])=[CH:4][C:3]=2[C:10]([F:13])([F:12])[F:11])[CH2:19][CH2:18][CH2:17][CH2:16][CH:15]=1

Participants

6

Reactant 3

HCID 38629021-Cyclohexenylboronic acidHCID 108006474-Bromo-3-(trifluoromethyl)benzonitrileHCID 10942334Sodium Methoxide

Product 1

HCID 592018284-(1-Cyclohexen-1-yl)-3-(trifluoromethyl)benzamideYield 78.9%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

4-bromo-3-(trifluoromethyl)benzonitrile (commercial) (1.2 g, 4.80 mmol), 1-cyclohexen-1-ylboronic acid (0.907 g, 7.20 mmol), sodium methoxide (0.778 g, 14.40 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.337 g, 0.480 mmol) were added to dry methanol (12 mL) and the mixture heated in the microwave at 80° C. for 10 minutes. The reaction mixture was partitioned between ethyl acetate (40 mL) and water (40 mL) and then the organic phase washed with further water (40 mL). The organic phase was dried (MgSO4), filtered and the solvent removed in vacuo. The crude product was purified by flash silica chromatography, eluting with 0-75% ethyl acetate in hexane to give the title compound as a white solid (1.02 g). δH (CDCl3, 400 MHz): 8.09 (1H, m), 7.90 (1H, dd), 7.32 (1H, d), 6.3-5.8 (2H, m) 5.61 (1H, s), 2.25-2.13 (4H, m), 1.80-1.60 (4H, m). MS (ES): C14H14F3NO requires 269; found 270 (MH+).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate (40 mL) and water (40 mL)
  2. washthe organic phase washed with further water (40 mL)
  3. dry with materialThe organic phase was dried (MgSO4)
  4. filtrationfiltered
  5. customthe solvent removed in vacuo
  6. customThe crude product was purified by flash silica chromatography
  7. washeluting with 0-75% ethyl acetate in hexane

Sources & evidence

ORD record
ord-f3c5e14589bf4bfb9f2874938cd25728
Source dataset
uspto-grants-2012_01
Patent number
US08101775B2

Reaction notes

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