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

HRID 715864노트

반응식

HRID 715864 반응식
C([O:3][C:4]([CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[N:13][C:14]([N:17]2[CH2:22][CH2:21][CH:20]([C:23]3[C:32]([CH:33]([F:44])[C:34]4[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:36][CH:35]=4)=[C:31]([CH:45]4[CH2:50][CH2:49][C:48]([F:52])([F:51])[CH2:47][CH2:46]4)[C:30]4[CH:29]([OH:53])[CH2:28][C:27]([CH3:55])([CH3:54])[CH2:26][C:25]=4[N:24]=3)[CH2:19][CH2:18]2)=[N:15][CH:16]=1)=[O:5])C.O1CCCC1.[OH-].[Na+].Cl>C(O)C>[C:4]([CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[N:15][C:14]([N:17]2[CH2:22][CH2:21][CH:20]([C:23]3[C:32]([CH:33]([F:44])[C:34]4[CH:35]=[CH:36][C:37]([C:40]([F:41])([F:42])[F:43])=[CH:38][CH:39]=4)=[C:31]([CH:45]4[CH2:46][CH2:47][C:48]([F:52])([F:51])[CH2:49][CH2:50]4)[C:30]4[CH:29]([OH:53])[CH2:28][C:27]([CH3:55])([CH3:54])[CH2:26][C:25]=4[N:24]=3)[CH2:19][CH2:18]2)=[N:13][CH:12]=1)([OH:5])=[O:3]

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 866824332-{1-[5-(4-Ethoxycarbonylbutoxy)pyrimidin-2-yl]piperidin-4-yl}-4-(4,4-difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol

생성물 1

HCID 76372467(-)-2-{1-[5-(4-Carboxybutoxy)pyrimidin-2-yl]piperidin-4-yl}-4-(4,4-difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol수율 64%

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

To the crude (−)-2-{1-[5-(4-Ethoxycarbonylbutoxyl)pyrimidin-2-yl]piperidin-4-yl}-4-(4,4-difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol obtained in Example (23-1), 2 ml of tetrahydrofuran, 2 ml of ethanol and 1 ml (1.00 mmol) of 1 N sodium hydroxide aqueous solution were added, and the reaction solution was stirred at room temperature for 1 hour. After completion of the reaction, 1 N hydrochloric acid was poured into the reaction solution under ice cooling and the reaction solution was extracted with methylene chloride. 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 purified by high performance liquid chromatography [YMC-pack ODS-A; acetonitrile/aqueous solution of 0.1% acetic acid and 0.1% triethylamine=85/15 (V/V)] to provide 63 mg of the title compound as a white solid (yield in two steps: 64%).

후처리

  1. additionwas poured into the reaction solution under ice cooling
  2. extractionthe reaction solution was extracted with methylene chloride
  3. washThe organic layer was washed with saturated sodium chloride aqueous solution
  4. dry with materialdried with anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe obtained residue was purified by high performance liquid chromatography [YMC-pack ODS-A; acetonitrile/aqueous solution of 0.1% acetic acid and 0.1% triethylamine=85/15 (V/V)]

출처 및 근거

ORD 기록
ord-70c090d9e4ed4758b1c8a193b92e73b0
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09187450B2

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