Dimethylformamide → N-(4-chloro-2-fluoro-3-formylphenyl)acetamide

Temperature

-78 °C

A −78° C. solution of N-(4-chloro-2-fluorophenyl)acetamide (2.00 g, 10.66 mmol) in THF (40 mL), under Ar, was treated with butyl lithium (16.66 mL, 26.7 mmol), stirred at −78° C. for 2.5 h, treated slowly with DMF (1.651 mL, 21.32 mmol), stirred for 15 min at −78° C. and slowly warmed to RT. The mixture was stirred for 2 h, treated with satd. NH4Cl, the layers separated and the aqueous layer extracted with EtOAc (1×). The combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex) to afford N-(4-chloro-2-fluoro-3-formylphenyl)acetamide (1.1 g, 48% yield) as an off-white solid. MS (ESI) m/z: 216.0 [M+H]+.

1. stirringstirred for 15 min at −78° C.
2. temperatureslowly warmed to RT
3. stirringThe mixture was stirred for 2 h
4. additiontreated with satd
5. customNH4Cl, the layers separated
6. extractionthe aqueous layer extracted with EtOAc (1×)
7. washThe combined organics were washed with brine
8. dry with materialdried over Na2SO4
9. concentrationconcentrated to dryness
10. custompurified via silica gel chromatography (EtOAc/Hex)

ORD record

ord-78f1b2ea7d4b4c97941d6bfe608d4b03

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08461179B1