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

HRID 1622077ノート

反応式

HRID 1622077 の反応式
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]

参加物

6

反応物 4

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

生成物 1

HCID 467397415-Fluoro-2-(methoxymethoxy)phenylboronic acid収率 72.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-884114235381410d944eeba7a0035d44
出典データセット
uspto-grants-2014_07
特許番号
US08778625B2

反応ノート

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