Thionyl Chloride → 3-[3-(6-Methyl-pyridin-3-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester

Participants

Reaction Steps

Compound K3 was prepared from 3-(6-methyl-pyridin-3-yl)-benzoic acid methyl ester [prepared by the following procedure: A mixture of 3-carboxyphenylboronic acid (4.82 g, 29.07 mmol) and 3-bromo-2-methylpyridine (5.00 g, 29.07 mmol) in acetonitrile (145 mL) and 0.4M Na2CO3-solution (145 mL) was degassed and Pd(Ph3P)4 (1.68 g, 5 mol %) was added. The reaction mixture was refluxed for 16 h, evaporated to dryness (cf. Synlett 6:829–831 (2000). The residue was suspended in MeOH (400 mL) and SOCl2 (10.5 mL, 145 mmol) was added dropwise at 23° C. and the reaction mixture was refluxed for 4 h. Evaporated to dryness, taken up in EtOAc, washed with sat. NaHCO3-solution and brine, dried over Na2SO4. Removal of the solvent in vacuum left a brown oil, which was purified by silica gel column chromatography with cyclohexane/EtOAc.] (3.87 g, 17.0 mmol) by treatment with lithium tert-butyl acetate according to general procedure K (method b). Starting from 3-(2-methyl-pyridin-4-yl)-benzoic acid methyl ester, prepared in analogy to the method described above, 3-[3-(2-Methyl-pyridin-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (Compound K4) was prepared in analogy to the above method.

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