Hydrochloric Acid → (5S)-4-(4,4-Difluorocyclohexyl)-2-[1-(5-{[(2S)-2,3-dihydroxypropyl]oxy}pyrimidin-2-yl)piperidin-4-yl]-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol

HRID 632615ノート

反応式

HRID 632615 の反応式
[F:1][C:2]1([F:54])[CH2:7][CH2:6][CH:5]([C:8]2[C:17]3[C@@H: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]([O:33][CH2:34][C@@H:35]5[CH2:39][O:38]C(C)(C)[O:36]5)=[CH:29][N:28]=4)[CH2:23][CH2:22]3)[C:9]=2[C@@H:42]([F:53])[C:43]2[CH:48]=[CH:47][C:46]([C:49]([F:52])([F:51])[F:50])=[CH:45][CH:44]=2)[CH2:4][CH2:3]1.Cl.[OH-].[Na+].[Cl-].[Na+]>CO>[F:54][C:2]1([F:1])[CH2:3][CH2:4][CH:5]([C:8]2[C:17]3[C@@H:16]([OH:18])[CH2:15][C:14]([CH3:19])([CH3:20])[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]([O:33][CH2:34][C@@H:35]([OH:36])[CH2:39][OH:38])=[CH:29][N:28]=4)[CH2:23][CH2:22]3)[C:9]=2[C@@H:42]([F:53])[C:43]2[CH:48]=[CH:47][C:46]([C:49]([F:50])([F:52])[F:51])=[CH:45][CH:44]=2)[CH2:6][CH2:7]1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 14798Sodium HydroxideHCID 89531585(5S)-4-(4,4-Difluorocyclohexyl)-2-[1-(5-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}pyrimidin-2-yl)piperidin-4-yl]-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol

生成物 1

HCID 71657166(5S)-4-(4,4-Difluorocyclohexyl)-2-[1-(5-{[(2S)-2,3-dihydroxypropyl]oxy}pyrimidin-2-yl)piperidin-4-yl]-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol収率 94%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
50 °C

実験手順

To a solution of 86.7 mg (0.114 mmol) of (5S)-4-(4,4-Difluorocyclohexyl)-2-[1-(5-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}pyrimidin-2-yl)piperidin-4-yl]-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol, which was prepared by a method similar to that of Reference Example 24, in 2 ml of methanol, 0.5 ml of 2 N hydrochloric acid was added, and the mixture was stirred at 50° C. for 2.5 hours. After completion of the reaction, 0.5 ml of 2 N sodium hydroxide aqueous solution was added to the reaction solution, then saturated sodium chloride aqueous solution was poured thereinto, and the reaction solution was extracted with ethyl acetate. The obtained organic phases were combined, washed with saturated sodium chloride aqueous solution, dried with magnesium sulfate and then filtered, and the solvent was distilled off under reduced pressure to provide 77.1 mg of the title compound as a white solid (yield: 94%).

後処理

  1. additionwas added to the reaction solution
  2. extractionthe reaction solution was extracted with ethyl acetate
  3. washwashed with saturated sodium chloride aqueous solution
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. distillationthe solvent was distilled off under reduced pressure

出典と根拠

ORDレコード
ord-c75a14563f5948d48ef9547508aeaabc
出典データセット
uspto-grants-2016_04
特許番号
US09321747B2

反応ノート

読み込み中…