Cesium fluoride → HCID 59781758, compound

HRID 2404337Notes

Reaction equation

HRID 2404337 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12].[F:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1B(O)O.[F-].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[F:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12]

Participants

8

Reactant 4

HCID 25953Cesium fluorideHCID 27343542-Fluorophenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 247213904-Bromo-3-(trifluoromethyl)benzoic acid

Product 1

HCID 59781758HCID 59781758, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
110 °C

Procedure

A mixture of 4-bromo-3-(trifluoromethyl)benzoic acid (15.0 g, 55.7 mmol), 2-fluorophenylboronic acid (9.4 g, 66.9 mmol), cesium fluoride (25.4 g, 167 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (5.7 g, 13.9 mmol) and palladium(II) acetate (1.25 g, 5.6 mmol) was prepared in dioxane (150 mL) and water (150 mL) under N2 atmosphere. The reaction mixture was purged with vacuum for 5 minutes, and then the reaction mixture was degassed with N2 at RT for 10 min. The reaction mixture was heated at 110° C. for 3 hours. The reaction mixture was cooled to RT and was filtered through a pad of Celite. The filtrate was concentrated under vacuum affording a yellow solid. After purification by flash chromatography (silica, DCM containing 1% of AcOH), the title compound was obtained as a pale yellow powder. HPLC (Method A), Rt 4.3 min (purity: 99.9%). LC/MS (Method B): 283.0 (M−H)−. 1H NMR (DMSO-d6, 300 MHz) δ 13.60 (s, 1H), 8.31 (d, J=1.4 Hz, 1H), 8.25 (dd, J=8.0, 1.4 Hz, 1H), 7.60 (d, J=8.0 Hz, 1H), 7.52 (m, 1H), 7.38-7.26 (m, 3H).

Workup

  1. customThe reaction mixture was purged with vacuum for 5 minutes
  2. customthe reaction mixture was degassed with N2 at RT for 10 min
  3. temperatureThe reaction mixture was cooled to RT
  4. filtrationwas filtered through a pad of Celite
  5. concentrationThe filtrate was concentrated under vacuum
  6. customaffording a yellow solid
  7. customAfter purification by flash chromatography (silica, DCM containing 1% of AcOH)

Sources & evidence

ORD record
ord-35b877a2bdca42ecb1ac07aa656a4cea
Source dataset
uspto-grants-2014_08
Patent number
US08802704B2

Reaction notes

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