Hydrochloric Acid → 5-(4-Chlorophenyl)-3-formylthiophene-2-carboxylic acid

Temperatur

0 °C

To a stirred solution 5-(4-chlorophenyl)thiophene-2-carboxylic acid (11 g, 0.046 mol) in dry THF (150 ml) was added n-BuLi (63 ml, 0.102 mol, 1.6 M solution in hexane) in a dropwise manner at −78° C. under inert atmosphere. The temperature was slowly raised to 0° C. over a period of 4 h. The reaction mixture was again cooled to −70° C. and dry DMF (34 ml, 0.43 mol) was added slowly. After completion of the addition of DMF, temperature was raised to −10° C. and stirred for 2 h. The reaction mixture was again cooled to −30° C. and 1.5 N HCl (50 ml) was added slowly and reaction was allowed to come to RT. The reaction mixture was extracted with EtOAc (4×200 ml). The combined organic layer washed with water (2×150 ml), brine (2×150 ml), dried (Na2SO4) and concentrated. The crude product washed with p-ether (100 ml) to afford 8 g of the title compound (65%). Rf=0.2 (CHCl3:MeOH, 8:2). This was found pure enough to carry further. Since this intermediate is unstable it has to be used immediately in the next step.

1. temperatureThe reaction mixture was again cooled to −70° C.
2. temperaturewas raised to −10° C.
3. temperatureThe reaction mixture was again cooled to −30° C.
4. customreaction
5. customto come to RT
6. extractionThe reaction mixture was extracted with EtOAc (4×200 ml)
7. washThe combined organic layer washed with water (2×150 ml), brine (2×150 ml)
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated
10. washThe crude product washed with p-ether (100 ml)

ORD-Eintrag

ord-73834b119e934d51933e61158474e563

Quelldatensatz

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07723331B2