Cesium carbonate → HCID 11739863、化合物

HRID 1866929ノート

反応式

HRID 1866929 の反応式
Br[C:2]1[C:3](=[O:26])[N:4]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].[C:27]([O-])([O-])=O.[K+].[K+].C([O-])([O-])=O.[Cs+].[Cs+].CB1OB(C)OB(C)O1>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:17][C:11]1[CH:12]=[C:13]([F:16])[CH:14]=[CH:15][C:10]=1[CH2:9][O:8][C:7]1[CH:6]=[CH:5][N:4]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=2)[C:3](=[O:26])[C:2]=1[CH3:27]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 102165503-bromo-4-(2,4-difluorobenzyloxy)-1-(3-fluorobenzyl)pyridin-2(1H)-one

生成物 1

HCID 11739863HCID 11739863、化合物収率 79%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 312751,4-Dioxane溶媒

実験手順

To a solution of 3-bromo-4-(2,4-difluorobenzyloxy)-1-(3-fluorobenzyl)-1H-pyridin-2-one (EXAMPLE 107) (0.14 g, 0.32 mmol), K2CO3 (88 mg, 0.64 mmol) and Cs2CO3 (0.10 g, 0.32 mmol) in dioxane (2 mL) was added Pd(PPh3)4 (18 mg, 0.12 mmol), followed by trimethylboroxine (40 mg, 0.32 mmol). The reaction mixture was degassed, purged with argon, and heated at reflux for 4 h. The reaction mixture was cooled to room temperature, and partitioned between water and EtOAc. The organic solution was washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent methylene chloride to 97:3 methylene chloride/MeOH) afforded 4-(2,4-difluorobenzyloxy)-1-(3-fluorobenzyl)-3-methyl-1H-pyridin-2-one as a white solid (0.09 g, 79%): mp 127-129° C.; 1H NMR (300 MHz, CDCl3) δ 7.50-7.40 (m, 1H), 7.35-7.25 (m, 1H), 7.17 (d, J=9 Hz, 1H), 7.06 (d, J=6 Hz, 1H), 7.00-6.80 (m, 4H), 6.12 (d, J=9 Hz, 1H), 5.12 (s, 4H), 2.07 (s, 3H). ESHRMS m/z 360.1180 (M+H C20H16F3NO2 requires 360.1206).

後処理

  1. customThe reaction mixture was degassed
  2. custompurged with argon
  3. temperatureheated
  4. temperatureat reflux for 4 h
  5. custompartitioned between water and EtOAc
  6. washThe organic solution was washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customPurification by flash column chromatography (silica, eluent methylene chloride to 97:3 methylene chloride/MeOH)

出典と根拠

ORDレコード
ord-c3259971f6334534957e7bd5bdd98fdd
出典データセット
uspto-grants-2009_12
特許番号
US07629363B2

反応ノート

読み込み中…