Potassium Carbonate → 3-[3-(6-Cyclopropyl-pyridin-3-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

Compound K7 was obtained from 3-(6-cyclopropyl-pyridin-3-yl)-benzonitrile [prepared by the following procedure: A mixture of 3-cyanophenylboronic acid [CAS-No. 150255-96-2] (8.82 g, 60 mmol), crude 5-bromo-2-cyclopropylpyridine {prepared by the following procedure: A mixture of 2,5-dibromopyridine (11.85 g, 50 mmol), cyclopropyl zinc chloride (0.4 M in THF, 160 mL, 64 mmol), Pd(PPh3)4 (578 mg, 1 mol %) in THF (55 mL) was stirred under Argon atmosphere at 70° C. for 1.5 h. Cooled to RT, poured into sat. NaHCO3-solution, extracted with ether, washed with brine, dried over Na2SO4. Removal of the solvent in vacuum left a brown oil (12.36 g).} (ca. 60 mmol), Pd(PPh3)4 (1.733 g, 3 mol %) and K2CO3 (13.82 g, 100 mmol) in toluene (250 mL), EtOH (22 mL) and H2O (50 mL) was stirred at 80° C. for 14 h. Cooled to RT, diluted with EtOAc, washed with sat. NaHCO3-solution and brine, dried over Na2SO4. Removal of the solvent in vacuum left a brown solid, which was purified by silica gel column chromatography with cyclohexane/-EtOAc.] (9.88 g, 44.87 mmol) by treatment with tert-butyl bromoacetate and activated zinc, followed by hydrolysis with 10% HCl according to general procedure K (method d).

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