Hydrochloric Acid → methyl (2E)-3-(4-{2-[2-(acetylamino)-1,3-thiazol-4-yl]vinyl}thiophen-2-yl)acrylate

Temperature

0 °C

To {[2-(acetylamino)-1,3-thiazol-4-yl]methyl}(triphenyl)phosphoniumchloride (6.602 g, 14.58 mmol) was added anhydrous N,N-dimethylformamide (30 ml), and the mixture was cooled to 0° C. Potassium tert-butoxide (3.146 g, 28.03 mmol) was added, and the mixture was stirred at 0° C. for 15 min. A solution of methyl (2E)-3-(4-formylthiophen-2-yl)acrylate (2.200 g, 11.21 mmol) in anhydrous N,N-dimethylformamide (30 ml) was added dropwise, and the mixture was stirred at 0° C. for 1 hr. The reaction mixture was poured into ice-cooled dil. hydrochloric acid (600 ml, containing 15 mmol as HCl). Sodium chloride (10 g) was added, and the mixture was extracted 3 times with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (FUJI SILYSIA CHEMICAL LTD. BW-300SP 500 g, ethyl acetate:hexane=1:1) to give methyl (2E)-3-(4-{2-[2-(acetylamino)-1,3-thiazol-4-yl]vinyl}thiophen-2-yl)acrylate (3.090 g, 9.241 mmol, 82.4%) as a yellowish-white solid.

1. stirringthe mixture was stirred at 0° C. for 1 hr
2. additionThe reaction mixture was poured into ice-
3. extractionthe mixture was extracted 3 times with ethyl acetate
4. washThe combined organic layer was washed with saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by silica gel column chromatography (FUJI SILYSIA CHEMICAL LTD. BW-300SP 500 g, ethyl acetate:hexane=1:1)

ORD record

ord-4fe7580cdc7640609dcd1f89699e5378

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507690B2