聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯] → 1-(2,4-Difluorophenyl)isoquinoline

HRID 8555

反应方程式

HRID 8555 反应方程式
[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

参与物

6

反应物 4

HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]HCID 11430碳酸钾HCID 1405391-氯异喹啉HCID 27343342,4-二氟苯硼酸

产物 1

HCID 219094191-(2,4-Difluorophenyl)isoquinoline

试剂、催化剂与溶剂 1

HCID 8071乙二醇二甲醚溶剂

实验过程

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).

后处理

  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

来源与证据

ORD记录
ord-08a08e084a414c518c9108c5bc2b198d
来源数据集
uspto-grants-2006_08
专利号
US07090929B2

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