3-PYRIDINEMETHANOL,6-CHLORO-5-FLUORO synthesis

Yield:1174028-24-0 41%

Reaction Conditions:

with formic acid;triethylamine;tetrakis(triphenylphosphine) palladium⁽⁰⁾ in 1,4-dioxane at 110; for 6 h;

Steps:

5.b

(b) (6-Chloro-5-fluoro-3-pyridinyl)methanolTo a solution of (2,6-dichloro-5-fluoro-3-pyridinyl)methanol (4.4 g, 22.45 mmol) in 1,4-dioxane (20 ml) was added Et₃N (3.42 ml, 24.69 mmol), formic acid (0.947 ml, 24.69 mmol) and Pd(PPh₃)₄ (1.297 g, 1.122 mmol). The mixture was then heated at 110° C. for 6 h in a pressure tube. The crude was diluted with H₂O and extracted twice with EtOAc. The combined organic phases were washed with H₂O and sat. NaCl, dried over Na₂SO₄ and concentrated under reduced pressure. The crude was purified by flash chromatography using Flashmaster II, a 70 g spherical silica gel cartridge and DCM/MeOH 98:2 as eluent to give 2.0 g (41%) of the title compound pure enough to be used in the next step.¹H-NMR (δ, ppm, CDCl₃): 8.18 (d, 1H), 7.70 (dd, 1H), 4.78 (bs, 2H), 1.93 (bs, 1H). [ES MS] m/z 162 (MH⁺).

References:

US2009/306089,2009,A1 Location in patent:Page/Page column 27