1,10-Phenanthroline → 4-(2,4-difluorobenzyloxy)-1H-pyridin-2-one

HRID 882053

反応式

HRID 882053 の反応式
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][OH:10].Cl[C:12]1[CH:17]=[C:16](I)[CH:15]=[CH:14][N:13]=1.C([O-])([O-])=[O:20].[Cs+].[Cs+].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1>C1(C)C=CC=CC=1.[Cu]I.C(O)=O.O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][O:10][C:16]1[CH:15]=[CH:14][NH:13][C:12](=[O:20])[CH:17]=1

参加物

8

反応物 4

HCID 13181,10-PhenanthrolineHCID 10796Cesium carbonateHCID 918672,4-Difluorobenzyl alcoholHCID 15165112-Chloro-4-iodopyridine

生成物 1

HCID 220503904-(2,4-difluorobenzyloxy)-1H-pyridin-2-one収率 44%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 1140Toluene溶媒HCID 18673298Formic acid--water (1/1)溶媒

反応条件

温度
105 °C

実験手順

A suspension of (2,4-difluorophenyl)methanol (4.86 g, 33.7 mmol), 2-chloro-4-iodopyridine (7.35 g, 30.7 mmol), Cs2CO3 (14.3 g, 43.8 mmol), CuI (5.83 g, 30.7 mmol) and 1,10-phenanthroline (1.11 g, 6.14 mmol) in toluene (20 mL) was degassed by bubbling N2 through the suspension for 15 min. The suspension was put under N2, and heated at 105° C. for 18 h. The suspension was cooled, EtOAc (50 mL) was added, and the resulting suspension was passed through a plug of SiO2. The resulting solution was concentrated under reduced pressure. Flash chromatography on silica gel (hexanes/(1:1 EtOAc/hexanes), 100:0 to 0:100) afforded a white solid. A suspension of the white solid and NH4OAc (8.21 g, 107 mmol) in 1:1 HCO2H/H2O (40 mL) was heated at reflux with stirring for 4 d. The solution was cooled and concentrated under reduced pressure. The resulting residue was made basic with saturated NaHCO3 solution, and the resulting suspension was filtered. The solid was washed with H2O and dried under reduced pressure to afford 3.16 g (44%) of the title compound as a white solid: 1H NMR (300 MHz, DMSO-d6) δ 11.14 (br s, 1H), 7.62 (br dd, J=15.3, 8.7 Hz, 1H), 7.33 (ddd, J=10.5, 10.5, 2.4 Hz, 1H), 7.25 (d, J=7.2 Hz, 1H), 7.12 (ddd, J=8.4, 8.4, 1.8 Hz, 1H), 5.91-5.82 (m, 2H), 5.06 (s, 2H).

後処理

  1. customwas degassed
  2. customby bubbling N2 through the suspension for 15 min
  3. temperatureThe suspension was cooled
  4. additionEtOAc (50 mL) was added
  5. concentrationThe resulting solution was concentrated under reduced pressure
  6. customFlash chromatography on silica gel (hexanes/(1:1 EtOAc/hexanes), 100:0 to 0:100) afforded a white solid
  7. temperaturewas heated
  8. temperatureat reflux
  9. temperatureThe solution was cooled
  10. concentrationconcentrated under reduced pressure
  11. filtrationthe resulting suspension was filtered
  12. washThe solid was washed with H2O
  13. customdried under reduced pressure

出典と根拠

ORDレコード
ord-0145a815c96d4349a087389612acb844
出典データセット
uspto-grants-2015_03
特許番号
US08993765B2

関連ノート

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