3-Chlorothiophene → 2-Acetyl-3-chlorothiophene

Temperature

-10 °C

To a solution of 3-chlorothiophene (4.80 g, 40.48 mmol) in THF (50 mL) was added BuLi (2.5N in hexane, 17.9 mL) at −30° C. After addition, the mixture was stirred for 30 min at −10° C., and then cooled to −45° C. N-methoxy-N-methyl acetamide (55.0 g, 48.8 mmol) was added and allowed to warm to room temperature during 40 min and maintained for an additional 20 min. Brine (80 mL) was added to quench the reaction, extracted with EA (60 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered, concentrated to afford 24-1 (˜80% pure) as a yellow oil (6.80 g) which used for the next step directly.

1. additionAfter addition
2. temperaturecooled to −45° C
3. temperatureto warm to room temperature during 40 min
4. temperaturemaintained for an additional 20 min
5. customto quench
6. customthe reaction
7. extractionextracted with EA (60 mL×3)
8. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
9. filtrationfiltered
10. concentrationconcentrated

ORD record

ord-205a27d2b5b54695bb0d25281f1778d2

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09180119B2