Sodium Methoxide → Methyl 4-bromo-5-fluoro-2-methoxybenzoate

Temperature

0 °C

A solution of methyl 4-bromo-2,5-difluorobenzoate (1.0 g, 3.98 mmol) in dry DMF (10 ml) was cooled down to 0° C. Sodium methoxide (25% in MeOH, 0.91 ml, 3.98 mmol) was dried with activated molecular sieves and slowly added to the starting material. The reaction mixture was stirred at 0° C. for 10 min and then at ambient temperature for 30 min. The mixture was then brought back to 0° C. and quenched with EtOAc (50 ml) and aqueous HCl (1 M, 50 ml). The phases were separated and the aqueous phase was extracted with EtOAc (2×100 ml), dried (Na2SO4), filtered and evaporated to give an oil. The crude product was purified by flash column chromatography (isooctane/EtOAc 9:1) gave the title compound (0.81 g, 75%). MS m/z (rel. intensity, 70 eV) 264 (M+, 30), 262 (M+, 31), 233 (65), 231 (bp), 229 (41).

1. additionslowly added to the starting material
2. waitat ambient temperature for 30 min
3. customwas then brought back to 0° C.
4. customquenched with EtOAc (50 ml) and aqueous HCl (1 M, 50 ml)
5. customThe phases were separated
6. extractionthe aqueous phase was extracted with EtOAc (2×100 ml)
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. customevaporated
10. customto give an oil
11. customThe crude product was purified by flash column chromatography (isooctane/EtOAc 9:1)

ORD record

ord-5b0654cd196c47a6afcf0fcab58510f1

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08492372B2