Cesium carbonate → 5-Fluoro-2-(3-methylsulfanyl-phenoxy)-nicotinic acid ethyl ester

Temperature

100 °C

A solution of ethyl-2-chloro-5-fluoro-nicotinoate (29 g, 0.143 mol) (prepared according to the method of J. Med. Chem., 1993, 36(18), 2676–88, at page 2684, column 2, 3rd compound, Ethyl 2-chloro-5-fluoropyridine-3-carboxylic acid) and 3-methylsulphanyl-phenol (20 g, 0.143 mol) (prepared according to the method of WO 98/45268, page 68, preparation 61) in dioxane (300 mL) was treated with caesium carbonate (46.5 g, 0.143 mol) at room temperature. The reaction mixture was heated to 100° C. and stirred for 48 hours. The reaction mixture was concentrated in vacuo and the residue taken up in water (600 mL) and extracted with ethyl acetate (3×250 mL). The organic layers were combined, washed with brine (200 mL), dried over magnesium sulphate and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:toluene (99.75:0.25 to 99.5:0.5) to yield the title product as a yellow oil, 27.1 g.

1. concentrationThe reaction mixture was concentrated in vacuo
2. extractionextracted with ethyl acetate (3×250 mL)
3. washwashed with brine (200 mL)
4. dry with materialdried over magnesium sulphate
5. concentrationconcentrated in vacuo
6. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane:toluene (99.75:0.25 to 99.5:0.5)

ORD record

ord-bd12f01d63714cc784fdec8a28b7ec68

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07153870B2