Acetaldehyde → HCID 58478774, compound

Temperature

-50 °C

A solution of thiophene-3-carboxylic acid (1.00 g, 7.8 mmol) in THF (10 mL) is added dropwise to a cold (−80° C.) solution of lithium bistrimethylsilylamide (8.6 mL of a 2M solution) in THF (15 mL). The resulting pale yellow solution is warmed to −50° C. and is stirred at −50° C. for 1 hr during which time a white precipitate is formed. The reaction mixture is cooled to −80° C. and treated dropwise with acetaldehyde (1.2 mL). The white precipitate gradually disappeared during the addition. The reaction mixture is warmed to −20° C. and stirred for 30 min. The reaction mixture is then poured into aqueous 2M HCl solution (120 mL). The resulting mixture is stirred at room temperature while a stream of air is blown into the reaction vessel to assist in the evaporation of THF. The white precipitate which forms is collected by filtration and dissolved in dichloromethane (5 mL) and Et3N (5 mL). The reaction mixture is treated with p-toluenesulfonyl chloride (0.38 g, 2.0 mmol) and stirred overnight. The reaction mixture is treated with NaHCO3 solution and the organic phase is collected, dried over Na2SO4, filtered and concentrated. The residue is purified by chromatography (silica gel) to give the title compound (0.39 g, 32%).

1. customis formed
2. temperatureThe reaction mixture is cooled to −80° C.
3. additionThe white precipitate gradually disappeared during the addition
4. temperatureThe reaction mixture is warmed to −20° C.
5. stirringstirred for 30 min
6. stirringThe resulting mixture is stirred at room temperature while a stream of air
7. customto assist in the evaporation of THF
8. filtrationThe white precipitate which forms is collected by filtration
9. dissolutiondissolved in dichloromethane (5 mL)
10. stirringstirred overnight
11. customthe organic phase is collected
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated
15. customThe residue is purified by chromatography (silica gel)

ORD record

ord-bcfd11a546234b21aed5573c45474e1b

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08455535B2