Dimethylformamide → HCID 83881329, compound

To a cold (−78° C.) solution of 2-Chloro-4-ethoxy-1-fluorobenzene (5.0 g, 28.6 mmol) in THF (100 mL) was added LDA (1.8 M in THF/heptane/ethylbenzene; 40 mL, 72 mmol). After 7 minutes, DMF (7 mL, 85.8 mmol) was added dropwise while keeping the temperature below −60° C. After 40 minutes, the reaction mixture was quenched with sat. aq. ammonium chloride. The organic layer was separated and the aq. layer was washed with ethyl acetate (2×50 mL). The combined organic layer was washed with water (30 mL) followed by brine. The organic layer was dried (Na2SO4) and concentrated to give a 1:1 mixture of the target compound and a regioisomeric aldehyde. The mixture was purified by column chromatography (5/95, ethyl acetate/hexanes) to give the title compound as a white solid. 1H NMR (CDCl3, 400 MHz): δ=1.46 (t, 3H, J=7.2 Hz), 4.11 (q, 2H, J=7.2 Hz), 6.84-6.86 (m, 1H), 7.25-7.28 (m, 1H), 10.48 (s, 1H).

1. customthe temperature below −60° C
2. waitAfter 40 minutes
3. customthe reaction mixture was quenched with sat. aq. ammonium chloride
4. customThe organic layer was separated
5. washthe aq. layer was washed with ethyl acetate (2×50 mL)
6. washThe combined organic layer was washed with water (30 mL)
7. dry with materialThe organic layer was dried (Na2SO4)
8. concentrationconcentrated
9. customto give
10. additiona 1:1 mixture of the target compound
11. customThe mixture was purified by column chromatography (5/95, ethyl acetate/hexanes)

ORD record

ord-62c04effe03c436394ca2cfca0ea0dd3

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08445510B2