Potassium Phosphate, Tribasic → 4-((1-Benzhydrylpiperidin-4-yl)methoxy) 5-cyclopropyl-2-fluorobenzoic acid

Temperatur

100 °C

A mixture of 4-((1-benzhydrylpiperidin-4-yl)methoxy)-5-chloro-2-fluorobenzoic acid (480 mg, 0.94 mmol), cyclopropylboronic acid (162 mg, 1.88 mmol), potassium phosphate (797 mg, 3.67 mmol), palladium acetate (21 mg, 0.047 mmol) and tricyclohexylphosphine tetrafluoroborate (36 mg, 0.094 mmol) in toluene (10 mL) and water (0.5 mL) was stirred under a nitrogen atmosphere at 100° C. for 18 h. The reaction mixture was cooled down, quenched with water (50 mL) and extracted with ethyl acetate (20 mL×3). The combined organic layers were washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated to afford product (320 mg, 46%, crude) as oil which was used in the next step without further purification. LCMS (ESI) m/z: 458.1 [M+H]+.

1. temperatureThe reaction mixture was cooled down
2. customquenched with water (50 mL)
3. extractionextracted with ethyl acetate (20 mL×3)
4. washThe combined organic layers were washed with brine (20 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customto afford product (320 mg, 46%, crude) as oil which
9. customwas used in the next step without further purification

ORD-Eintrag

ord-7554cdfe36ff4f6ebcab8d8c3332aa14

Quelldatensatz

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08952169B2