Triethylamine → Methyl 5-chloro-2-fluoro-4-methylbenzoate

Temperature

80 °C

To a solution of 1-bromo-5-chloro-2-fluoro-4-methylbenzene (10 g, 44.7 mmol) in 200 mL of methanol were added 1,1′-binaphthalene-2,2′-diylbis(diphenylphosphine)-dichloropalladium (1:1) (358 mg, 0.447 mmol) and N,N-diethylethanamine (8.11 mL, 58.2 mmol). The resulting reaction mixture was placed in a bomb, pressurised to 80 psi of carbon monoxide and heated at 80° C. for 18 hours. The reaction mixture was concentrated in vacuo to yield a semi-solid which was dissolved in EtOAc (300 mL) and washed with water (200 mL). The organic layer was separated, dried over magnesium sulfate, filtered and evaporated in vacuo. The resulting crude product was purified by silica gel chromatography eluting with 0 to 20% EtOAc in heptane to afford the title compound as a white crystalline solid (8.47 g, 93%).

1. customThe resulting reaction mixture
2. concentrationThe reaction mixture was concentrated in vacuo
3. customto yield a semi-solid which
4. washwashed with water (200 mL)
5. customThe organic layer was separated
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. customevaporated in vacuo
9. customThe resulting crude product was purified by silica gel chromatography
10. washeluting with 0 to 20% EtOAc in heptane

ORD record

ord-0f3ab62d38c149bcb9748bb1e89e2f9e

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09102621B2