Cesium fluoride → Methyl 3'-fluoro-2-(methoxymethyl)-2'-methylbiphenyl-4-carboxylate

温度

100 °C

A mixture of methyl 4-bromo-3-(methoxymethyl)benzoate (Intermediate 1, Step 2, 5.00 g, 19.3 mmol), 3-fluoro-2-methylphenylboronic acid (4.46 g, 29.0 mmol), bis(triphenylphosphine)palladium(II) chloride (271 mg, 0.39 mmol) and cesium fluoride (8.79 g, 57.9 mmol) was prepared in dioxane (50 mL) and water (20 mL) under nitrogen atmosphere. The reaction mixture was heated at 100° C. for 1 hour. The reaction mixture was cooled at RT, diluted with MTBE (250 mL) and the layers were separated. The organic layer was washed with water (100 mL) and brine (100 mL). The aqueous layers were extracted with MTBE (150 mL). The organic layers were combined, dried over MgSO4 and concentrated under reduced pressure. After purification by flash chromatography (silica, EtOAc/n-hexane), the title compound was obtained as a colorless oil (4.85 g, 87%). HPLC (Method A), Rt 5.0 min (purity: 99.5%). LC/MS (Method B): 289.0 (M+H)+.

1. temperatureThe reaction mixture was cooled at RT
2. customthe layers were separated
3. washThe organic layer was washed with water (100 mL) and brine (100 mL)
4. extractionThe aqueous layers were extracted with MTBE (150 mL)
5. dry with materialdried over MgSO4
6. concentrationconcentrated under reduced pressure
7. customAfter purification by flash chromatography (silica, EtOAc/n-hexane)

ORDレコード

ord-0cf5d2f1c2c84bc3b2a455209f39cd07

出典データセット

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08815919B2