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

HRID 1044787

반응식

HRID 1044787 반응식
N#N.Br[C:4]1[CH:9]=[CH:8][C:7]([Br:10])=[C:6]([F:11])[C:5]=1[F:12].[Li]CCCC.[C:18](=O)=[O:19].S(C)C>CCOCC.CC(=O)OCC.Cl.C1COCC1.O>[Br:10][C:7]1[CH:8]=[CH:9][C:4]([CH2:18][OH:19])=[C:5]([F:12])[C:6]=1[F:11]

참가 물질

11

반응물 5

HCID 280Carbon DioxideHCID 947NitrogenHCID 1068Dimethyl SulfideHCID 184623931,4-Dibromo-2,3-difluorobenzeneHCID 178418339Butyllithium

생성물 1

HCID 66819962(4-Bromo-2,3-difluorophenyl)methanol

시약·촉매·용매 5

HCID 313Hydrochloric Acid용매HCID 962Water용매HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매2회

반응 조건

온도
-78 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-29f1f2bbc0674747868b1961c7e30f6d
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08563714B2

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