Sodium Carbonate → (E)-2-Bromo-4-(2,5-difluorostyryl)-5-fluoropyridine

HRID 2362410노트

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HRID 2362410 반응식
[Br:1][C:2]1[CH:7]=[C:6](B(O)O)[C:5]([F:11])=[CH:4][N:3]=1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=1[CH:20]=[CH2:21].C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Br:1][C:2]1[CH:7]=[C:6](/[CH:21]=[CH:20]/[C:14]2[CH:15]=[C:16]([F:19])[CH:17]=[CH:18][C:13]=2[F:12])[C:5]([F:11])=[CH:4][N:3]=1

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 218718902,5-DifluorostyreneHCID 44631046(2-Bromo-5-fluoropyridin-4-yl)boronic acid

생성물 1

HCID 86673436(E)-2-Bromo-4-(2,5-difluorostyryl)-5-fluoropyridine

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매

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온도
50 °C

실험 절차

A suspension of 2-bromo-5-fluoropyridin-4-ylboronic acid (1.569 g, 7.14 mmol) and 1,4-difluoro-2-vinylbenzene (1 g, 7.14 mmol) in dimethylformamide (20 mL) was flushed with a balloon of oxygen. To this was added sodium carbonate (1.51 g, 14.3 mmol) and palladium(II) acetate (0.16 g, 0.71 mmol) as solids in one portion. The flask was flushed with another balloon of oxygen and fitted with a balloon of oxygen. The reaction was warmed to 50° C. After 1 h, the reaction was treated with a second portion of sodium carbonate (0.75 g) and boronic acid (1.6 g). This process was repeated twice more (total boronic acid addition=6.3 g). The reaction was cooled to room temperature, diluted with ether, washed with water (3×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (2.5%→5% EtOAc/Hex) gave 89 mg (4.0%) as a white solid. 1H NMR (CDCl3) Shift: 8.28 (d, J=1.8 Hz, 1H), 7.68 (d, J=5.5 Hz, 1H), 7.49 (d, J=16.5 Hz, 1H), 7.33 (ddd, J=8.9, 5.8, 3.1 Hz, 1H), 7.17 (d, J=16.8 Hz, 1H), 6.98-7.14 (m, 2H). 19F NMR (CDCl3) Shift: −118.54 (d, J=13.0 Hz, 1F), −122.71 (br. s., 1F), −135.71 (br. s., 1F). Mass spec.: 314.0 (MH)+.

후처리

  1. customwas flushed with a balloon of oxygen
  2. customThe flask was flushed with another balloon of oxygen
  3. customfitted with a balloon of oxygen
  4. additionthe reaction was treated with a second portion of sodium carbonate (0.75 g) and boronic acid (1.6 g)
  5. addition(total boronic acid addition=6.3 g)
  6. temperatureThe reaction was cooled to room temperature
  7. additiondiluted with ether
  8. washwashed with water (3×)
  9. dry with materialbrine, dried over magnesium sulfate
  10. concentrationconcentrated
  11. customColumn chromatography (2.5%→5% EtOAc/Hex) gave 89 mg (4.0%) as a white solid

출처 및 근거

ORD 기록
ord-8b865149f148479fa42156c999021f92
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08691821B2

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