Methyl formate → 5-Bromo-2-fluorobenzaldehyde

To a solution of N,N-diisopropylamine (8.87 mL, 62.9 mmol, 1.1 eq) in dry THF (80 mL) at −78° C. was added n-BuLi (2.5M in hexane, 27.5 mL, 68.5 mmol, 1.2 eq). The resulting mixture was stirred for 30 min then 1-bromo-4-fluoro-benzene (10 g, 57.1 mmol, 1 eq) in dry THF (20 mL) was added. The resultant mixture was stirred at −78° C. for 2 h then methyl formate (3.8 g, 62.9 mmol, 1.1 eq) was added and the reaction was stirred a further 30 min at −78° C. The reaction was allowed to warm to room temperature and stirred a further 1 h. The reaction was then diluted with water (100 mL), and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (petroleum ether:EtOAc, 20:1) to give the title compound as a yellow oil (6.25 g, 54%).

1. stirringthe reaction was stirred a further 30 min at −78° C
2. stirringstirred a further 1 h
3. extractionthe aqueous layer was extracted with EtOAc
4. washThe combined organic extracts were washed with brine
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. customevaporated in vacuo
8. customThe residue obtained
9. customwas purified by column chromatography (petroleum ether:EtOAc, 20:1)

ORD record

ord-e63c2de607204b52916b9b755b669efb

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249085B2