6-(3-Trifluoromethylphenyl)pyridine-3-carboxaldehyde synthesis

Yield:898405-21-5 36%

Reaction Conditions:

with sodium carbonate;tetrakis(triphenylphosphine) palladium⁽⁰⁾ in 1,2-dimethoxyethane;water; for 18 h;Heating / reflux;

Steps:

25.i

i) 6-(3-Trifluoromethyl-phenyl)-pyridine-3-carbaldehyde 1.44 g (1.25 mmol) Pd(PPh₃)₄ was added under argon at room temperature to a solution of 6-bromo-pyridine-3-carbaldehyde in 60 ml 1,2 dimethoxyethane and stirred for 15 min. 63 ml (125 mmol) of 2 M sodium carbonate solution and 2.5 g (13.16 mmol)of 3-(trifluoromethyl-)-phenylboronic acid were added and the mixture heated to boiling temperature for 18 hours (h). The reaction mixture was cooled to room temperature, filtered, and the filtrate evaporated. The residue was taken up with ethyl acetate, washed twice with water, dried over sodium sulphate and evaporated. Chromatography on silica (eluent: ethyl acetate/n-heptane 1:3) gave 1.18 g (36%) of 6-(3-Trifluoromethyl-phenyl)-pyridine-3-carbaldehyde MS: 252.1 (ESI+) ¹H-NMR(400 Hz, [D₆]DMSO): δ=7.86(t, 1H, Ar-CF), 7.95(d, 1H, Ar-CF), 8.43(t, 2H, pyridine), 8.57(d, 1H, Ar-CF), 8.57(s, 1H, Ar-CF), 9.26(s, 1H, pyridine), 10.23(s, 1H, CHO),

References:

US2007/32530,2007,A1 Location in patent:Page/Page column 21