Hydrochloric Acid → 3-Fluoro-4-(trifluoromethoxy)benzeneboronic acid

HRID 552028노트

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HRID 552028 반응식
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([O:9][C:10]([F:13])([F:12])[F:11])=[C:5]([F:14])[CH:4]=1.[B:15](OC)([O:18]C)[O:16]C.Cl>C1COCC1.C(OCC)(=O)C>[F:14][C:5]1[CH:4]=[C:3]([B:15]([OH:18])[OH:16])[CH:8]=[CH:7][C:6]=1[O:9][C:10]([F:13])([F:12])[F:11]

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 8470Trimethyl borateHCID 27822174-Bromo-2-fluoro-1-(trifluoromethoxy)benzeneHCID 5462224Magnesium

생성물 1

HCID 27831933-Fluoro-4-(trifluoromethoxy)benzeneboronic acid수율 54.1%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매3회HCID 8857Ethyl Acetate용매

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온도
55 °C

실험 절차

Well-dried magnesium (3.05 g) and THF (20.0 ml) were put in a reaction vessel under a nitrogen atmosphere, and heated to 55° C. Then, 1-bromo-3-fluoro-4-trifluoromethoxybenzene (T-13; 25.0 g) dissolved in THF (100 ml) was slowly added dropwise thereto in the temperature range of 47° C. to 60° C., and stirred for additional 60 minutes. The obtained Grignard reagent was added dropwise to trimethyl borate (14.0 g) in a THF (100 ml) solution in the temperature range of −74° C. to −65° C., and stirred for additional 180 minutes while allowing temperature to come to 25° C. After the reaction mixture had been cooled to −30° C., 6N-hydrochloric acid (90 ml) was slowly added dropwise and stirred for additional 180 minutes while temperature was allowed to come to 25° C. Then, the reaction mixture was poured into a vessel containing ice-water (250 ml) and 3,000 ml, and mixed. Ethyl acetate (300 ml) was added to separate the mixture into organic and aqueous layers, and an extraction operation was carried out. The obtained organic layer was fractionated, washed sequentially with water, a saturated aqueous solution of sodium bicarbonate and brine, and then dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure, whereby 11.7 g of 3-fluoro-4-trifluoromethoxy phenylboronic acid (T-14) was obtained. The yield based on the compound (T-13) was 54%.

후처리

  1. additionwas slowly added dropwise
  2. stirringstirred for additional 180 minutes
  3. customto come to 25° C
  4. temperatureAfter the reaction mixture had been cooled to −30° C.
  5. stirringstirred for additional 180 minutes while temperature
  6. customto come to 25° C
  7. additionThen, the reaction mixture was poured into a vessel
  8. additionmixed
  9. customto separate the mixture into organic and aqueous layers
  10. washwashed sequentially with water
  11. dry with materiala saturated aqueous solution of sodium bicarbonate and brine, and then dried over anhydrous magnesium sulfate
  12. distillationThen, the solvent was distilled off under reduced pressure

출처 및 근거

ORD 기록
ord-be00afe93c694a12ba9d5d46442ce186
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07951433B2

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