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 632615노트

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HRID 632615 반응식
[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

참가 물질

6

반응물 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

생성물 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-ol수율 94%

시약·촉매·용매 1

HCID 887Methanol용매

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온도
50 °C

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-c75a14563f5948d48ef9547508aeaabc
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321747B2

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