Reaction #9421

Reaction equation

2-bromo-3-methylthiophene

diethylamine

n-BuLi

DMF

→

title compound

5-Bromo-4-methyl-2-thiophene carboxaldehyde

Solvents

THF

THF

hexane

Conditions

Workup

1. 1
   workup.ADDITIONAfter addition
2. 2
   Temperaturecooled to −78° C.
3. 3
   workup.STIRRINGThe reaction solution was stirred at −78° C. for 30 minutes
4. 4
   Temperatureto warm to ambient temperature
5. 5
   Otherwas quenched with 1N aqueous hydrochloride solution (1 L)
6. 6
   ExtractionThe solution was extracted with ethyl acetate (3×450 mL)
7. 7
   Washthe extracts washed with water, brine
8. 8
   Dryingdried (MgSO4)
9. 9
   OtherAfter removal of solvent in vacuo

Procedure

To a solution of diethylamine (28 g, 0.383 mol) in anhydrous THF (400 mL) was added at −40° C. under nitrogen a solution of n-BuLi (2.5 M, 153 mL, 0.383 mol) in hexane. After addition, the solution was stirred at −40° C. under nitrogen for 30 minutes, cooled to −78° C. and treated dropwise with a solution of 2-bromo-3-methylthiophene (45 g, 0.254 mol) in anhydrous THF (450 mL). The reaction solution was stirred at −78° C. for 30 minutes and treated with anhydrous DMF (100 mL). The mixture was allowed to warm to ambient temperature and was quenched with 1N aqueous hydrochloride solution (1 L). The solution was extracted with ethyl acetate (3×450 mL) and the extracts washed with water, brine and dried (MgSO4). After removal of solvent in vacuo, the title compound was obtained as a white solid (46 g, 88.3%). A sample of the product was crystallized from hexane: mp 63–65° C.; IR (KBr) 1654 cm−1. 1H-NMR (CDCl3) δ 9.75 (s, 1H), 7.45 (s, 1H), 2.26 (s, 3H); MS (EI) m/z 204/206 (M+). Anal. Calc. For C6H5BrOS: C, 35.14; H, 2.46. Found: C, 35.00; H, 2.44.

Source