5-Bromothiophene-2-carbaldehyde → 2-(5-Bromothiophen-2-yl)-1-(2-chlorophenyl)-2-hydroxyethan-1-one

Temperature

40 °C

Under an atmosphere of nitrogen, to a clod (−78° C.) solution of lithium bis(trimethylsilyl)amide (8.05 mL, 1.0M solution in THF, 8.05 mmol) was added a solution of (2-chloro-phenyl)-trimethylsilanyloxy-acetonitrile (1.69 g, 7 mmol) in tetrahydrofuran (10 mL) dropwise over 10 min. After stirring for another 30 min, a solution of 5-bromothiophen-2-carboxaldehyde in tetrahydrofuran (10 mL) was added dropwise. The reaction was stirred overnight from −78° C. to reach room temperature, then was quenched by adding 3N HCl (20 mL) and warming at 40° C. for 5 hrs. After cooling, the mixture was partitioned between ethyl ether and water. The organic layer was stirred with 1M NaOH (30 mL) for 2 hrs; and the layers were separated. The organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The crude product was purified by chromatography on silica gel (Hexane/EtOAc, 8/2) to give a brown oil (320 mg, 14% yield). 1H-NMR (400 MHz, CDCl3): δ 4.35 (d, 1H), 6.12 (d, 1H), 7.02 (d, 1H), 7.26 (m, 2H), 7.41 (d, 1H), 7.44 (dd, 1H).

1. stirringThe reaction was stirred overnight from −78° C.
2. customto reach room temperature
3. customwas quenched
4. additionby adding 3N HCl (20 mL)
5. temperatureAfter cooling
6. customthe mixture was partitioned between ethyl ether and water
7. stirringThe organic layer was stirred with 1M NaOH (30 mL) for 2 hrs
8. customand the layers were separated
9. washThe organic layer was washed with brine
10. dry with materialdried over Na2SO4
11. concentrationconcentrated in vacuo
12. customThe crude product was purified by chromatography on silica gel (Hexane/EtOAc, 8/2)

ORD record

ord-24b202ccd810440cba273399ba53b1ff

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09000022B2