Ethanol → 6-(4-Fluorophenyl)picolinic acid

HRID 347533

반응식

HRID 347533 반응식
Br[C:2]1([C:8]([OH:10])=[O:9])[CH:7]=[CH:6][CH:5]=[CH:4][NH:3]1.C([O-])([O-])=O.[Na+].[Na+].[F:17][C:18]1[CH:23]=[CH:22][C:21](B2OCC(C)(C)CO2)=[CH:20][CH:19]=1.CCO>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:4]2[N:3]=[C:2]([C:8]([OH:10])=[O:9])[CH:7]=[CH:6][CH:5]=2)=[CH:20][CH:19]=1

참가 물질

7

반응물 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 110200772-(4-Fluorophenyl)-5,5-dimethyl-1,3,2-dioxaborinaneHCID 210815642-Bromo-picolinic acid

생성물 1

HCID 210817086-(4-Fluorophenyl)picolinic acid수율 46%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
100 °C

실험 절차

A solution of 2-bromo-picolinic acid (2.02 g, 10 mmol, Aldrich) in DME containing 4 mL of 10% aq. Na2CO3 was purged with Ar gas, treated with Pd(PPh3)4 followed by 2-(4-fluorophenyl)-5,5-dimethyl-1,3,2-dioxaborinane (2.40 g, 11.5 mmol, Aldrich) and EtOH (20 mL). This mixture was then also purged with Ar gas. The reaction mixture was heated at 100° C. for 2.5 h in a sealed tube. Additional 2-bromo-picolinic acid (900 mg) and Pd(PPh3)4 was added, and after purging with Ar gas it was heated at 100° C. for 4.5 h. Trifluoroacetic acid (20 mL) was added to the reaction and the mixture was concentrated in vacuo. MeOH (150 mL) was added to the residue and the insoluble material was filtered. The filtrate was concentrated in vacuo, and the resulting residue was purified by flash column chromatography on silica gel eluting with EtOAc/MeOH (9:1) followed by EtOAc/MeOH/HOAc (14:30:1) to afford the desired product (1.0 g, 40% based on borinane starting material) as a white solid. 1H NMR (CD3OD) δ 8.01 (d, 1H, J=7.7 Hz), 7.94–7.87 (m, 3H), 7.73 (d, 1H, J=7.7 Hz), 7.13 (t, 2H, J=8.8 Hz); MS(ESI+) m/z 234 (M+H)+.

후처리

  1. customThis mixture was then also purged with Ar gas
  2. additionAdditional 2-bromo-picolinic acid (900 mg) and Pd(PPh3)4 was added
  3. customafter purging with Ar gas it
  4. temperaturewas heated at 100° C. for 4.5 h
  5. additionTrifluoroacetic acid (20 mL) was added to the reaction
  6. concentrationthe mixture was concentrated in vacuo
  7. additionMeOH (150 mL) was added to the residue
  8. filtrationthe insoluble material was filtered
  9. concentrationThe filtrate was concentrated in vacuo
  10. customthe resulting residue was purified by flash column chromatography on silica gel eluting with EtOAc/MeOH (9:1)

출처 및 근거

ORD 기록
ord-b9303d3f1b8b444da8f1484c9e9e9c1a
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07173031B2

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