Sodium hydride → HCID 9825424, compound

Participants

Reaction Steps

1.0 g (3.2 mmol) of 4-methoxy-3-(4-methylthiomethyloxytetrahydrofuran-3-yloxy)benzoic acid (starting compound A19) are heated to reflux for 90 min in 4 ml of oxalyl chloride. Excess oxalyl chloride is removed in vacuo and coevaporated using 2×20 ml of toluene. A solution of 520 mg (3.2 mmol) of 4-amino-3,5-dichloropyridine in 10 ml of tetrahydrofuran is added dropwise to a suspension of 200 mg (6.9 mmol) of 80% strength sodium hydride in 10 ml of tetrahydrofuran. The mixture is stirred at RT for 90 min, then the acid chloride is added dropwise in a further 10 ml of tetrahydrofuran and the reaction mixture is stirred at RT for 2 h. It is concentrated, the residue is treated with 25 ml of water and the mixture is extracted with 3×25 ml of ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution, dried over magnesium sulfate, concentrated and the residue is chromatographed on silica gel. The product-containing fractions are concentrated and the residue is crystallized from acetonitrile. 300 mg of the title compound of m.p. 195-198° C. are obtained.

Provenance & Evidence