Water → (-)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-2-{1-[5-(2-methylpropoxy)pyrimidine-2-yl]piperidin-4-yl}-5,6,7,8-tetrahydroquinoline-5-ol

HRID 715861ノート

反応式

HRID 715861 の反応式
[F:1][C:2]1([F:46])[CH2:7][CH2:6][CH:5]([C:8]2[C:17]3[CH:16]([OH:18])[CH2:15][C:14]([CH3:20])([CH3:19])[CH2:13][C:12]=3[N:11]=[C:10]([CH:21]3[CH2:26][CH2:25][N:24]([C:27]4[N:32]=[CH:31][C:30]([OH:33])=[CH:29][N:28]=4)[CH2:23][CH2:22]3)[C:9]=2[CH:34]([F:45])[C:35]2[CH:40]=[CH:39][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:37][CH:36]=2)[CH2:4][CH2:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].I[CH2:54][CH:55]([CH3:57])[CH3:56].O>O1CCCC1>[F:46][C:2]1([F:1])[CH2:3][CH2:4][CH:5]([C:8]2[C:17]3[CH:16]([OH:18])[CH2:15][C:14]([CH3:19])([CH3:20])[CH2:13][C:12]=3[N:11]=[C:10]([CH:21]3[CH2:22][CH2:23][N:24]([C:27]4[N:32]=[CH:31][C:30]([O:33][CH2:54][CH:55]([CH3:57])[CH3:56])=[CH:29][N:28]=4)[CH2:25][CH2:26]3)[C:9]=2[CH:34]([F:45])[C:35]2[CH:36]=[CH:37][C:38]([C:41]([F:43])([F:42])[F:44])=[CH:39][CH:40]=2)[CH2:6][CH2:7]1

参加物

6

反応物 4

HCID 962WaterHCID 10556Isobutyl iodide3 回HCID 10796Cesium carbonate3 回HCID 76372263(-)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-2-[1-(5-hydroxypyrimidin-2-yl)piperidin-4-yl]-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol

生成物 1

HCID 76372465(-)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-2-{1-[5-(2-methylpropoxy)pyrimidine-2-yl]piperidin-4-yl}-5,6,7,8-tetrahydroquinoline-5-ol収率 68.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
50 °C

実験手順

To a solution of 55 mg (0.085 mmol) of (−)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-2-[1-(5-hydroxypyrimidin-2-yl)piperidin-4-yl]-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol, which was prepared by a method similar to that of Example 4, in 1 ml of tetrahydrofuran, 33 mg (0.10 mmol) of cesium carbonate and 11 μl (0.094 mmol) of 1-iodo-2-methyl propane were added, and the reaction solution was stirred at room temperature for 2 hours, at 50° C. for 3 hours and further at room temperature for 14 hours. After stirring at room temperature, 50 (0.43 mmol) of 1-iodo-2-methyl propane and 50 mg (0.15 mmol) of cesium carbonate were added and the reaction solution was stirred at 70° C. for 9 hours. After stirring with heating, 50 μl (0.43 mmol) of 1-iodo-2-methyl propane and 100 mg (0.31 mmol) of cesium carbonate were further added and the reaction solution was stirred at room temperature for 14.5 hours. After completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and dried with anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was subjected to silica gel column chromatography [n-hexane/ethyl acetate=95/5-70/30 (V/V)] and the fraction including the desired compound was concentrated under reduced pressure. n-Hexane was added to the obtained residue and the precipitate was obtained by filtration to provide 41 mg of the title compound as a white solid (yield: 68%).

後処理

  1. stirringAfter stirring at room temperature
  2. stirringthe reaction solution was stirred at 70° C. for 9 hours
  3. stirringAfter stirring
  4. temperaturewith heating
  5. stirringthe reaction solution was stirred at room temperature for 14.5 hours
  6. customAfter completion of the reaction
  7. extractionextracted with ethyl acetate
  8. washThe organic layer was washed with saturated sodium chloride aqueous solution
  9. dry with materialdried with anhydrous magnesium sulfate
  10. distillationthe solvent was distilled off under reduced pressure
  11. concentrationwas concentrated under reduced pressure
  12. additionn-Hexane was added to the obtained residue
  13. customthe precipitate was obtained by filtration

出典と根拠

ORDレコード
ord-473b86ae38844de689de461e4e12034c
出典データセット
uspto-grants-2015_11
特許番号
US09187450B2

反応ノート

読み込み中…