Hydrochloric Acid → 5-Bromo-3-chlorothiophene-2-carboxylic acid

Temperatur

0 °C

To a solution of DIPA (26.3 g, 0.26 mol) in 400 mL of dry THF was added a solution of n-BuLi (104 mL, 0.26 mol, 2.5M in n-hexane) at −78° C. under nitrogen. After the addition was completed, the mixture was stirring for 1 h and then warmed to 0° C. and stirred for 30 min. To above LDA solution was added a solution of 3-chlorothiophene-2-carboxylic acid (21 g, 0.13 mol) in THF (50 mL) at −78° C. After stirring for 1 h, a solution of 1,2-dibromo-ethane (48.9 g, 0.26 mmol) in THF (50 mL) was added at −78° C. The mixture was stirred at −78° C. for 1.5 h and slowly warm to RT. The mixture was poured into aq. HCl solution, and then extracted with EtOAc. The combined extracts were dried over Na2SO4, concentrated to give 25 g of 5-bromo-3-chlorothiophene-2-carboxylic acid. MS (M+H): 241, 243. 1H NMR (400 MHz, DMSO-d6): δ 7.50 (s, 1H).

1. additionAfter the addition
2. stirringstirred for 30 min
3. stirringAfter stirring for 1 h
4. stirringThe mixture was stirred at −78° C. for 1.5 h
5. temperatureslowly warm to RT
6. extractionextracted with EtOAc
7. dry with materialThe combined extracts were dried over Na2SO4
8. concentrationconcentrated

ORD-Eintrag

ord-072eb756f1444cc1834596a8f35e3745

Quelldatensatz

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09181236B2