Water → 2-But-3-enyl-2-thiophen-2-yl-hex-5-enoic acid ethyl ester

Temperature

-78 °C

Ethyl 2-(thiophen-2-yl)acetate (2.35 g) was dissolved in tetrahydrofuran (30 mL) and cooled to −78° C. Lithium bis(trimethylsilyl)amide (2.31 g) in THF (1M solution, 13.8 mL) was added and the solution was stirred for 30 minutes. 4-Bromo-but-1-ene (1.4 mL) was added and the reaction mixture was allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was re-cooled to −78° C. and lithium bis(trimethylsilyl)amide (2.31 g) in THF (1M solution, 13.8 mL) was added and the solution was stirred for 30 minutes. 4-Bromo-but-1-ene (1.4 mL) was added and the reaction mixture was allowed to warm to room temperature and stand overnight. HPLC-MS analysis indicated that the reaction was incomplete so the reaction was again cooled to −78° C. and further aliquots of lithium bis(trimethylsilyl)amide (1M solution, 10 mL) and 4-bromo-but-1-ene (1.0 mL) were added following the procedure outlined above. After stirring for a further 2 hours, water (30 mL) was added and the reaction was extracted with diethyl ether (2×60 mL). The combined organic extracts were dried (MgSO4) and evaporated. The resulting oil was purified by column chromatography on silica eluting with ethyl acetate/isohexane (1/99) afford the sub-titled compound (3.18 g).

1. temperatureto warm to room temperature
2. stirringstirred for 1 hour
3. temperatureThe reaction mixture was re-cooled to −78° C.
4. stirringthe solution was stirred for 30 minutes
5. temperatureto warm to room temperature
6. waitstand overnight
7. temperaturewas again cooled to −78° C.
8. stirringAfter stirring for a further 2 hours
9. extractionthe reaction was extracted with diethyl ether (2×60 mL)
10. dry with materialThe combined organic extracts were dried (MgSO4)
11. customevaporated
12. customThe resulting oil was purified by column chromatography on silica eluting with ethyl acetate/isohexane (1/99)

ORD record

ord-f013eb2b8dea4eb1b968c70d5c23ac5d

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08329729B2