Potassium Phosphate, Tribasic → HCID 86703757, compound

Temperature

130 °C

To a solution of tert-butyl 4-butoxy-5-chloro-2-fluorobenzoate (0.23 g, 0.76 mmol), cyclopropylboronic acid (0.10 g, 1.14 mmol), potassium phosphate (0.64 g, 3.10 mmol) and tricyclohexylphosphine tetrafluoroborate (0.05 g, 0.15 mmol) in toluene (3 mL) and water (0.3 mL) under a nitrogen atmosphere was added palladium acetate (0.005 g, 0.076 mmol). The reaction mixture was heated at 130° C. for 30 minutes in the microwave then cooled to ambient temperature. Water (20 mL) was added and the mixture extracted with ethyl acetate (2×15 mL). The combined organics were washed with brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (5% ethyl acetate in hexanes) afforded tert-butyl 4-butoxy-5-cyclopropyl-2-fluorobenzoate (0.15 g, 67%), which was used directly in the next step. To a solution of this compound (0.15 g, 0.48 mmol) in dichloromethane (2 mL), was added trifluoroacetic acid (2 mL). The reaction mixture was stirred at room temperature for 1 hour and then concentrated in vacuo. The residue was triturated in diethyl ether (10 mL) and the solid was filtered, rinsed with diethyl ether (2×10 mL) and dried to give the title compound (0.048 g, 40%). 1H NMR (300 MHz, CDCl3) δ 7.48 (d, J=8.3 Hz, 1H), 6.56 (d, J=12.7 Hz, 1H), 4.08-3.95 (m, 2H), 2.18-0.39 (m, 14H).

1. temperaturethen cooled to ambient temperature
2. extractionthe mixture extracted with ethyl acetate (2×15 mL)
3. washThe combined organics were washed with brine
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated in vacuo
6. customPurification of the residue by column chromatography (5% ethyl acetate in hexanes)

ORD record

ord-d0c8ad3a84034661b888aa5c232fa968

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952169B2