Methyl formate → 2-Chloro-3-fluoro-6-methoxybenzaldehyde

To a solution of 3-chloro-4-fluoroanisole (28.5 g, 178 mmol) in t-butyl methyl ether (200 mL, dried over anhydrous MgSO4) at −78° C. was added 2.5 M n-butyl lithium in hexanes (107 mL, 267.5 mmol). After 3 h, methyl formate (18.76 mL) was added drop-wise while keeping the temperature below −60° C. The reaction mixture was quenched with sat. aq. ammonium chloride (250 mL) after 45 minutes and the organic layer was separated. The aq. layer was extracted with ethyl acetate (2×100 mL) and the combined organic layer was washed with water (200 mL) followed by brine, dried (Na2SO4) and concentrated to give a residue which on trituration with hexanes gave solids. The solids were filtered, taken again in hexanes and heated over steam bath. It was cooled, the light yellow desired product filtered and air dried to give the title compound. 1H NMR (400 MHz, CDCl3): δ=10.48 (d, J=0.8 Hz, 1H), 7.31 (dd, J=9.4, 7.8 Hz, 1H), 6.88 (dd, J=7.8, 3.8 Hz, 1H), 3.92 (s, 3H).

1. customthe temperature below −60° C
2. customThe reaction mixture was quenched with sat. aq. ammonium chloride (250 mL) after 45 minutes
3. customthe organic layer was separated
4. extractionThe aq. layer was extracted with ethyl acetate (2×100 mL)
5. washthe combined organic layer was washed with water (200 mL)
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated
8. customto give a residue which on trituration with hexanes
9. customgave solids
10. filtrationThe solids were filtered
11. temperatureheated over steam bath
12. temperatureIt was cooled
13. filtrationthe light yellow desired product filtered
14. customair dried

ORD record

ord-8a8c115cc71249739eb9365a03779cb0

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08445510B2