Carbon Dioxide → (4-Bromo-2,3-difluorophenyl)methanol

温度

-78 °C

In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 1,4-dibromo-2,3-difluorobenzene (490 mg, 1.80 mmol) in dry Et2O (6 mL) was added to a n-BuLi (0.72 mL of a 2.5M solution in hexanes, 1.80 mmol) at −78° C. The reaction mixture was stirred at −78° C. for 2 h before solid CO2 was added. The reaction mixture was stirred at −78° C. for 10 min and then allowed to warm up to rt. The mixture was then diluted with EA and aq. 1N HCl was added. The layers separated and the org. layer dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give the crude carboxylic acid as a pale yellow solid. The crude material (360 mg, 1.52 mmol) was dissolved in dry THF (7 mL) and treated with BH3.Me2S complex (1.0 M in THF, 3.0 mL, 3.00 mmol) at 0° C. The reaction mixture was then warmed to 50° C. and stirred at this temperature until completion of the reaction. The mixture was cooled to 0° C. and water was added followed by EA. The layers were separated and the aq. layer extracted with EA (3×). The combined org. extracts were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by FC (hept-EA 9:1 to 2:1) to give the title compound as a colorless oil. TLC:rf (1:1 EA-hept)=0.50.

1. additionwas added
2. temperatureto warm up to rt
3. additionwas added
4. customThe layers separated
5. dry with materiallayer dried over MgSO4
6. filtrationfiltered
7. customthe solvents were removed under reduced pressure
8. customto give the crude carboxylic acid as a pale yellow solid
9. additiontreated with BH3
10. customat 0° C
11. temperatureThe reaction mixture was then warmed to 50° C.
12. stirringstirred at this temperature until completion of the reaction
13. temperatureThe mixture was cooled to 0° C.
14. customThe layers were separated
15. extractionthe aq. layer extracted with EA (3×)
16. washextracts were washed with brine
17. dry with materialdried over MgSO4
18. filtrationfiltered
19. concentrationconcentrated under reduced pressure
20. customThe crude residue was purified by FC (hept-EA 9:1 to 2:1)

ORDレコード

ord-29f1f2bbc0674747868b1961c7e30f6d

出典データセット

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08563714B2