Triethylamine → Nicotinic Acid

This example illustrates the preparation of Compounds 62, 106, 107, and 109, an example of reduction of a α-hydroxyhaloheterocyclomethyl derivative to the α-hydroxyheterocyclomethyl derivative, and oxidation of this derivative to compounds of the present invention. A mixture of methyl 5-[(2-chloro-5-thiazolyl)-hydroxymethyl)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate (7.2 g, 16 mmol), 6 mL triethylamine, and 5% of palladium on activated carbon catalyst (5 g) in 80 mL methanol was placed in a Parr hydrogenation apparatus at 50 psi and RT for 18 h. The reaction mixture was filtered through celite. The celite was thoroughly washed with methanol. The combined filtrates was concentrated in vacuo. The residual solid was purified by flash chromatography on silica gel with 30% ethyl acetate-cyclohexane to afford 3-pyridinecarboxylic acid, 2-(difluoromethyl)-5-(hydroxy-5-thiazolylmethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-, methyl ester (5 g, 73.5%) as A light yellow solid. m.p. 140°-150° C.

1. filtrationThe reaction mixture was filtered through celite
2. washThe celite was thoroughly washed with methanol
3. concentrationThe combined filtrates was concentrated in vacuo
4. customThe residual solid was purified by flash chromatography on silica gel with 30% ethyl acetate-cyclohexane

ORD record

ord-fddada19b9d84661b35017f4c0ece919

Source dataset

uspto-grants-1993_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05260262