Cesium fluoride → HCID 66718285, compound

HRID 2404326Notes

Reaction equation

HRID 2404326 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH2:12][O:13][CH3:14].[F:15][C:16]([F:27])([F:26])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1B(O)O.[F-].[Cs+].C1(P(C2CCCCC2)C2(OC)CC=CC(OC)=C2C2C=CC=CC=2)CCCCC1>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:14][O:13][CH2:12][C:3]1[CH:4]=[C:5]([C:6]([O:8][CH3:9])=[O:7])[CH:10]=[CH:11][C:2]=1[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[C:16]([F:27])([F:26])[F:15]

Participants

8

Reactant 4

HCID 25953Cesium fluorideHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 58554220Methyl 4-bromo-3-(methoxymethyl)benzoate2×HCID 665453372-Dicyclohexylphosphino-2,6-dimethoxybiphenyl

Product 1

HCID 66718285HCID 66718285, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of methyl 4-bromo-3-(methoxymethyl)benzoate (Intermediate 1 Step 2, 8.0 g, 30.8 mmol), 2-(trifluoromethyl)phenylboronic acid (8.8 g, 46.3 mmol), cesium fluoride (14.0 g, 92.4 mmol), palladium acetate (0.69 g, 3.1 mmol) and 2-dicyclohexylphosphino-2,6-dimethoxybiphenyl (3.16 g, 7.7 mmol) was prepared in a mixture of dioxane (80 mL) and water (80 mL) under nitrogen atmosphere and heated at 100° C. for 12 hours. The reaction mixture was concentrated under vacuum. The residue was diluted with EtOAc (200 mL), and then washed with water (100 mL) and brine (100 mL). The organic layer was dried (Na2SO4) and concentrated under vacuum. After purification by flash chromatography (silica, pet ether/EtOAc), the title compound was obtained as a pale yellow solid (8.0 g, 88%). 1H NMR (CDCl3, 400 MHz) δ 8.22 (1H, s), 7.99 (1H, d, J=6.5 Hz), 7.78 (1H, d, J=7.7 Hz), 7.57 (2H, m), 7.27 (2H, m), 4.19-4.10 (2H, m), 3.95 (3H, s), 3.26 (3H, s).

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. additionThe residue was diluted with EtOAc (200 mL)
  3. washwashed with water (100 mL) and brine (100 mL)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. concentrationconcentrated under vacuum
  6. customAfter purification by flash chromatography (silica, pet ether/EtOAc)

Sources & evidence

ORD record
ord-978b06dc5c5b4b30a1bb62053335fba7
Source dataset
uspto-grants-2014_08
Patent number
US08802704B2

Reaction notes

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