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

Temperature

80 °C

To a solution of 1-bromo-5-chloro-2-fluoro-4-methylbenzene (Comm, 10 g, 44.7 mmol) in methanol (200 mL) was 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 mixture was placed in a bomb and pressurized with carbon monoxide to 80 psi and heated at 80° C. for 18 hours. The reaction mixture was then 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 sulphate, filtered and concentrated in vacuo to yield an orange oil, which solidified on standing (9.87 g). The solid was purified by silica gel chromatography eluting with 0 to 20% EtOAc in heptane to afford the title compound as a crystalline white solid (8.47 g, 93%).

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

ORD record

ord-e9c5bcda29134b399834cabad3a11163

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096500B2