Sodium Carbonate → Methyl 5-fluoro-2-(pyrimidin-2-yl)benzoate

HRID 1524893노트

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HRID 1524893 반응식
[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1B1OC(C)(C)C(C)(C)O1.Cl[C:22]1[N:27]=[CH:26][CH:25]=[CH:24][N:23]=1.C(=O)([O-])[O-].[Na+].[Na+]>O>[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[C:22]1[N:27]=[CH:26][CH:25]=[CH:24][N:23]=1

참가 물질

5

반응물 3

HCID 10340Sodium CarbonateHCID 744042-ChloropyrimidineHCID 67086953Methyl 5-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate

생성물 1

HCID 67086501Methyl 5-fluoro-2-(pyrimidin-2-yl)benzoate수율 35%

시약·촉매·용매 1

HCID 962Water용매

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온도
74 °C

실험 절차

To a 250 mL round-bottomed flask, was added 5-fluoro-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzoic acid methyl ester (5.9 g, 21.06 mmol) in 2-methyl-THF (50 mL). To the resulting solution was added 2-chloropyrimidine (2.9 g, 25.28 mmol), sodium carbonate (6.7 g, 63.19 mmol), and water (17 mL). The mixture was degassed for 30 minutes. PdCl2(dppf)-dcm adduct (CAS#72287-26-4) (0.688 g, 0.843 mmol) was added and the reaction mixture was degassed once more for 30 minutes. The reaction mixture was warmed to 74° C. and stirred overnight. To the resulting solution was added diethyl ether (100 mL) and water (100 mL). The layers were thoroughly mixed then separated. The aqueous layer was extracted with additional diethyl ether (100 mL). The combined organics were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to a brown crude material (5.85 g, 49% desired, 2.87 actual product). The crude product was further purified through recrystallization in 10% EtOAc/hexanes. The mixture was warmed to 70° C. and cooled slowly to room temperature. After filtration, the desired product was obtained as a brown solid (1.72 g actual product, 35% yield overall after recrystallization.) 1H NMR (400 MHz, CDCl3): 8.78 (d, J=4.9 Hz, 2H), 8.09 (dd, J=8.7, 5.5 Hz, 1H), 7.39 (dd, J=8.6, 2.7 Hz, 1H), 7.30-7.20 (m, 2H), 3.77 (s, 3H).

후처리

  1. customThe mixture was degassed for 30 minutes
  2. customthe reaction mixture was degassed once more for 30 minutes
  3. additionTo the resulting solution was added diethyl ether (100 mL) and water (100 mL)
  4. additionThe layers were thoroughly mixed
  5. customthen separated
  6. extractionThe aqueous layer was extracted with additional diethyl ether (100 mL)
  7. dry with materialThe combined organics were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure to a brown crude material (5.85 g, 49% desired, 2.87 actual product)
  10. customThe crude product was further purified through recrystallization in 10% EtOAc/hexanes
  11. temperatureThe mixture was warmed to 70° C.
  12. temperaturecooled slowly to room temperature
  13. filtrationAfter filtration

출처 및 근거

ORD 기록
ord-46c94dd23a0e45858e6cb57e9898e58e
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09079911B2

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