Thionyl Chloride → (E)-N-[4-chloro-3-(pyridin-4-ylmethoxy)-phenyl]-3-(3-acetoxy-4-methoxy-phenyl)-acrylamide

Temperature

35 °C

A solution (E)-3-(3-acetoxy-4-methoxy-phenyl)-acrylic acid (0.20 g, 0.76 mmol) and thionyl chloride (0.069 mL, 0.95 mmol) in dry THF (4 mL) was stirred at reflux temperature for 2.5 hrs. Then a further aliquot of thionyl chloride (0.008 mL, 0.11 mmol) was added and the mixture was stirred at reflux temperature for additional 5 hrs. After cooling to about 35° C., a solution of 4-chloro-3-(pyridin-4-ylmethoxy)-phenylamine (0.232 mg, 0.99 mmol) and diisopropylethylamine (0.54 mL, 3.04 mmol) in dry THF (0.5 mL) was added dropwise. After stirring at reflux temperature for 2 hrs, the reaction mixture was diluted with DCM and washed with water, aqueous sodium hydrogencarbonate, and brine. The organic layer was then dried over sodium sulphate and evaporated. The resulting raw material was purified by column chromatography over silica gel (eluant DCM/MeOH 98/2) to give 250 mg of the title (E)-N-[4-chloro-3-(pyridin-4-ylmethoxy)-phenyl]-3-(3-acetoxy-4-methoxy-phenyl)-acrylamide as a light brown solid.

1. temperatureat reflux temperature for 2.5 hrs
2. temperatureat reflux temperature for additional 5 hrs
3. stirringAfter stirring
4. temperatureat reflux temperature for 2 hrs
5. washwashed with water, aqueous sodium hydrogencarbonate, and brine
6. dry with materialThe organic layer was then dried over sodium sulphate
7. customevaporated
8. customThe resulting raw material was purified by column chromatography over silica gel (eluant DCM/MeOH 98/2)

ORD record

ord-7eca32caffbb42979b2b0a1cc2792863

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08669261B2