Citric Acid → 5-Fluoro-2-(methoxymethoxy)phenylboronic acid

HRID 1622077노트

반응식

HRID 1622077 반응식
C([Li])CCC.Br[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[O:14][CH2:15][O:16][CH3:17].C[O:19][B:20](OC)[O:21]C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[CH3:17][O:16][CH2:15][O:14][C:8]1[CH:9]=[CH:10][C:11]([F:13])=[CH:12][C:7]=1[B:20]([OH:21])[OH:19]

참가 물질

6

반응물 4

HCID 311Citric AcidHCID 8470Trimethyl borateHCID 220325852-Bromo-4-fluoro-1-(methoxymethoxy)benzeneHCID 178418339Butyllithium

생성물 1

HCID 467397415-Fluoro-2-(methoxymethoxy)phenylboronic acid수율 72.7%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-78 °C

실험 절차

A 500 mL round bottom flask was charged with a 1.6 M solution of n-butyllithium in hexanes (100 mL, 0.16 mol) and flushed with nitrogen. The solution was cooled to −78° C. and a solution of 2-bromo-4-fluoro-1-methoxymethoxy-benzene (30.1 g, 0.13 mol) in dry tetrahydrofuran (50 mL) was added dropwise over one hour. The mixture was stirred at −78° C. and then trimethylborate (20 mL, 0.175 mol) was added very slowly via syringe. The reaction was allowed to gradually warm to room temperature and after two hours the mixture was poured into ice. The mixture was acidified to pH 4 with 5% aqueous citric acid and extracted with ethyl acetate (×3). The combined organic extracts were washed with water and brine, dried over MgSO4 and filtered. The solvent was evaporation under reduced pressure and the residue was recrystallized from hexanes give 2-methoxymethoxy-5-fluorophenylboronic acid (18.9 g).

후처리

  1. customflushed with nitrogen
  2. temperatureto gradually warm to room temperature and after two hours the mixture
  3. additionwas poured into ice
  4. extractionextracted with ethyl acetate (×3)
  5. washThe combined organic extracts were washed with water and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporation under reduced pressure
  9. customthe residue was recrystallized from hexanes

출처 및 근거

ORD 기록
ord-884114235381410d944eeba7a0035d44
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08778625B2

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