Water → Diethyl 2-[(2,5-dichloro-3-thienyl)methyl]malonate

Temperature

0 °C

To a stirred solution of sodium hydride (60% oil dispersion, 7.6 g, 190 mmol) in DMF (32 mL) was added a solution of diethyl malonate (35.2 g, 220 mmol) in THF (120 mL) at 0° C. and the mixture was stirred for 30 min at 0° C. To the mixture was added a solution of 3-(bromomethyl)-2,5-dichlorothiophene (26.9 g, 110 mmol) in THF (50 mL) at −35° C. over 1.5 hours. After stirring at −35° C. for 2 hours, the reaction mixture was poured into water and the whole extracted with ethyl acetate (200 mL×3). The combined organic layer was washed with water (200 mL), brine (200 mL), dried over MgSO4 and concentrated in vacuo. Fractionally distillation of the residue under reduced pressure (bp 150° C., 1.0 mmHg) provided the subtitle compound (28.6 g, 80% yield).

1. stirringAfter stirring at −35° C. for 2 hours
2. extractionthe whole extracted with ethyl acetate (200 mL×3)
3. washThe combined organic layer was washed with water (200 mL), brine (200 mL)
4. dry with materialdried over MgSO4
5. concentrationconcentrated in vacuo
6. distillationFractionally distillation of the residue under reduced pressure (bp 150° C., 1.0 mmHg)

ORD record

ord-d5cd76e53eb94170ba0bf3cca0ab5ad7

Source dataset

uspto-grants-2004_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06696470B2