Cesium fluoride → HCID 58554189, compound

Temperature

90 °C

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 to 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 over 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%). LC/MS (Method B): 297.0 (M+H)+. 295.0 (M−H)−.

1. waitAfter 15 hours
2. temperaturethe reaction mixture was cooled to 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 over MgSO4
6. concentrationconcentrated under reduced pressure
7. customAfter purification by flash chromatography (silica, EtOAc/heptane)

ORD record

ord-ad7101ada65b4ef1bc52785412218fbe

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802704B2