methyl 5-(3-(trifluoromethyl)phenyl)pyridine-3-carboxylate synthesis

Yield:-

Reaction Conditions:

with potassium phosphate;tetrakis(triphenylphosphine) palladium⁽⁰⁾ in 1,4-dioxane;water at 100; for 6 h;

Steps:

11.1

Example 11; Preparation of c?-l-(4-inethyl-6-(ljff-pyrazol-5-ylamino)pyrimidin~2-yl]-5-[3-(trifluoroniethyl)phenyl]piperdine-3-carboxylic acid trifluoroacetate Step 1: Preparation of methyl 5-[3-(trifluoromethyl)phenyl]nicotmateMethyl 5-bromonicotinate (168.2 mg), 3-trifluoromethylbenzeneboromc acid (165.6 mg), K₃PO₄ (378.5 mg) and Pd(PPh₃)₄ (92.2 mg) was mixed in dioxane (5 ml). To the suspension was added water (0.25 ml). And the mixture was heated to 100 ⁰C under stirring. After 6 hours, the mixture was cooled to room temperature and was diluted with EtOAc. The insoluble material was filtered off and washed with EtOAc. The filtrate was poured into saturated aqueous solution OfNaHCO₃ and extracted with EtOAc. The extract was washed with brine, dried over MgSO₄ and concentrated. The residue was purified with silica gel column chromatography (eluent : hexane / EtOAc - 94 / 6 ~ 50 / 50) to give methyl 5-[3- (trifluoromethyl)phenyl]nicotmate (190.1 mg) as a pale yellow solid.¹H NMR (400 MHz₃ CDCl₃) δ 4.01 (3H, s), 7.65 (IH, t), 7.71 (IH, d), 7.81 (IH, d), 7.87 (IH, s), 8.51 (IH, t), 9.02 (IH, d), 9.25 (IH, d) ESI-MS m/z 282.1 [M+Hf.

References:

WO2010/111056,2010,A1 Location in patent:Page/Page column 38-39