Water → 1-(2,4-Difluorophenyl)isoquinoline

HRID 8555

반응식

HRID 8555 반응식
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1B(O)O.Cl[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][N:14]=1.C(=O)([O-])[O-].[K+].[K+].O>C(COC)OC>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][N:14]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 140539Isoquinoline, 1-chloro-HCID 27343342,4-Difluorophenylboronic acid

생성물 1

HCID 219094191-(2,4-Difluorophenyl)isoquinoline

시약·촉매·용매 1

HCID 80711,2-Dimethoxyethane용매

실험 절차

2,4-difluorophenylboronic acid (Aldrich Chemical Co., 13.8 g, 87.4 mmol), 1-chloroisoquinoline (Adrich Chemical Co., 13 g, 79.4 mmol), tetrakistriphenylphosphine palladium(0) (Aldrich, 3.00 g, 2.59 mmol), potassium carbonate (EM Science, 24.2 g, 175 mmol), water (300 mL), and dimethoxyethane (Aldrich, 300 mL) were allowed to stir at reflux for 20 h under N2, after which time the mixture was cooled to room temperature and the organic and aqueous layers were separated. The aqueous layer was extracted with 3×150 mL of diethyl ether, and the combined organic fractions were dried with sodium sulfate, filtered, and the filtrate was evaporated to dryness. The crude material was chromatographed on a silica gel column, first by eluting the catalyst byproduct with 4:1 hexanes/CH2Cl2, and finally the product was eluted with CH2Cl2/MeOH (9.5:0.5, product Rf=0.7). The pure product fractions were collected and dried in vacuo, to afford 17.7 g (92% isolated yield) of a light yellow solid, >95% pure NMR spectroscopy. 1H NMR (CDCl3, 296 K, 300 MHz): δ 8.61 (1H, d, J=5.7 Hz), 7.89 (1H, d, J=8.2 Hz), 7.67–7.85 (3H, m), 7.52–7.63 (2H, m), 6.95–7.12 (2H, m) ppm. 19F NMR (CDCl3, 296K, 282 MHz) δ −109.01 (1F, brs), −109.87 (1F, d, JF-F=8.5 Hz).

후처리

  1. temperatureat reflux for 20 h under N2
  2. customthe organic and aqueous layers were separated
  3. extractionThe aqueous layer was extracted with 3×150 mL of diethyl ether
  4. dry with materialthe combined organic fractions were dried with sodium sulfate
  5. filtrationfiltered
  6. customthe filtrate was evaporated to dryness
  7. customThe crude material was chromatographed on a silica gel column
  8. washfirst by eluting the catalyst byproduct with 4:1 hexanes/CH2Cl2
  9. washfinally the product was eluted with CH2Cl2/MeOH (9.5:0.5, product Rf=0.7)
  10. customThe pure product fractions were collected
  11. customdried in vacuo
  12. customto afford
  13. custom17.7 g (92% isolated yield) of a light yellow solid, >95% pure NMR spectroscopy

출처 및 근거

ORD 기록
ord-08a08e084a414c518c9108c5bc2b198d
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07090929B2

연결된 노트

불러오는 중…