Cesium fluoride → HCID 58554189, compound

HRID 1630996Notes

Reaction equation

HRID 1630996 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[OH:12].[F:13][C:14]([F:25])([F:24])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1B(O)O.[F-].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>O1CCOCC1.CC(OC)(C)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[OH:12][C:3]1[CH:4]=[C:5]([C:6]([O:8][CH3:9])=[O:7])[CH:10]=[CH:11][C:2]=1[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[C:14]([F:25])([F:24])[F:13]

Participants

9

Reactant 4

HCID 25953Cesium fluorideHCID 27343872-(Trifluoromethyl)benzeneboronic acid3×HCID 6425184Methyl 4-Bromo-3-hydroxybenzoateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl3×

Product 1

HCID 58554189HCID 58554189, compound

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalyst3×HCID 962WaterSolventHCID 15413tert-Butyl methyl etherSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of methyl 4-bromo-3-hydroxybenzoate (Combi-Blocks CA-4189, 4.00 g, 17.3 mmol), 2-(trifluoromethyl)phenylboronic acid (3.95 g, 20.8 mmol), cesium fluoride (7.90 g, 52 mmol), palladium(II) acetate (78 mg, 0.35 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (426 mg, 1.05 mmol) was prepared in dioxane (40 mL) and water (20 mL) under N2 atmosphere. The reaction mixture was heated at 90° C. After 90 minutes, additional amounts of 2-(trifluoromethyl)phenylboronic acid (1.90 g, 10 mmol), palladium(II) acetate (78 mg, 0.35 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (426 mg, 1.05 mmol) were added. After 45 additional minutes, additional amounts of 2-(trifluoromethyl)phenylboronic acid (2.7 g, 14.2 mmol), palladium(II) acetate (78 mg, 0.35 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (426 mg, 1.05 mmol) were added. After 15 hours, the reaction mixture was cooled at RT, diluted with MTBE (200 mL), and then washed with water (30 mL) and brine (50 mL). The aqueous layers were extracted with MTBE (100 mL). The organic layers were combined, dried (MgSO4) and concentrated under reduced pressure. After purification by flash chromatography (silica, EtOAc/heptane), the title compound was obtained as a yellow oil (5.03 g containing 12% w/w of DCM). HPLC (Method A), Rt: 3.6 min (purity: 98.8%). UPLC/MS, M+(ESI): 297.0, M−(ESI): 295.0.

Workup

  1. waitAfter 15 hours
  2. temperaturethe reaction mixture was cooled at RT
  3. washwashed with water (30 mL) and brine (50 mL)
  4. extractionThe aqueous layers were extracted with MTBE (100 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customAfter purification by flash chromatography (silica, EtOAc/heptane)

Sources & evidence

ORD record
ord-0a2f3a5aaa0c4a6491d7f39aae3819cd
Source dataset
uspto-grants-2014_07
Patent number
US08791142B2

Reaction notes

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