Carbon Dioxide → 3-Bromo-2-fluoro-5-methylbenzoic acid

温度

-10 °C

To a solution of diisopropylamine (1.8 mL, 12.7 mmol) in THF (20 mL) at −10° C., n-BuLi (0.68 g, 10.6 mmol) was added and the reaction was stirred for 1 hour at −10° C. and was then cooled to −78° C. A solution of 2-bromo-1-fluoro-4-methylbenzene (2.0 g, 10.6 mmol) in THF (10 mL) was added in dropwise and the reaction was stirred for 1 hour after which excess solid carbon dioxide (4.76 g, 106 mmol) was added. After 30 minutes the reaction mixture was allowed to warm to room temperature, allowing for pressure release, and was quenched with water. The resulting layers were separated and the aqueous portion was extracted with Et2O. The aqueous layer was then acidified with aqueous 6.0 M HCl solution and the resulting white precipitate was extracted into Et2O. The combined organic portions were dried (MgSO4), and concentrated in vacuo to afford 3-bromo-2-fluoro-5-methylbenzoic acid (2.1 g, 9.0 mmol, 85%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 2.37 (s, 3H) 7.60 (dd, J=5.9, 1.8 Hz, 1H) 7.75 (dd, J=6.2, 1.8 Hz, 1H).

1. temperaturewas then cooled to −78° C
2. additionwas added
3. waitAfter 30 minutes the reaction mixture was allowed
4. temperatureto warm to room temperature
5. customwas quenched with water
6. customThe resulting layers were separated
7. extractionthe aqueous portion was extracted with Et2O
8. extractionthe resulting white precipitate was extracted into Et2O
9. dry with materialThe combined organic portions were dried (MgSO4)
10. concentrationconcentrated in vacuo

ORDレコード

ord-52735d4b6cef4cfcbf6b7064b7102bd3

出典データセット

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08859548B2