2-Ethylthiophene → 5-Bromo-2-methoxyphenyl-5-ethyl-2-thienylmethanol

Temperature

-78 °C

A solution of 2-ethylthiophene (3.00 g) in tetrahydrofuran (36 ml) was cooled to 0° C. under argon atmosphere, and thereto was added dropwise n-butyl lithium (1.56 M hexane solution, 17.1 ml). The mixture was stirred at the same temperature for 30 minutes, and cooled to −78° C., and thereto was added dropwise a suspension of 5-bromo-2-methoxybenzaldehyde (5.74 g) in tetrahydrofuran (60 ml). The mixture was stirred at the same temperature for 2 hours, warmed to 0° C., and thereto was added a saturated aqueous ammonium chloride solution. The mixture was extracted with ethyl acetate, and the extract was washed with brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0-85:15) to give 5-bromo-2-methoxyphenyl-5-ethyl-2-thienylmethanol (5.99 g) as a pale yellow syrup. APCI-Mass m/Z 309/311 (M+H—H2O). (2) The above 5-bromo-2-methoxyphenyl-5-ethyl-2-thienylmethanol was treated in a manner similar to Reference Example 1-(2) to give 5-bromo-(5-ethyl-2-thienylmethyl)-2-methoxybenzene as oil. APCI-Mass m/Z 311/313 (M+H).

1. additionwas added dropwise
2. stirringThe mixture was stirred at the same temperature for 2 hours
3. temperaturewarmed to 0° C.
4. extractionThe mixture was extracted with ethyl acetate
5. washthe extract was washed with brine
6. dry with materialdried over sodium sulfate
7. customThe solvent was evaporated under reduced pressure
8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0-85:15)

ORD record

ord-06e143d2aa87472caa1882f372213d91

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08222219B2