Hydrochloric Acid → (5S)-4-(4,4-Difluorocyclohexyl)-2-[1-(5-{[(2R)-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 632617Notes

Reaction equation

HRID 632617 reaction equation
[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

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 14798Sodium HydroxideHCID 89683079HCID 89683079, compound

Product 1

HCID 71657169(5S)-4-(4,4-Difluorocyclohexyl)-2-[1-(5-{[(2R)-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-olYield 99%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 108.4 mg (0.142 mmol) of (5S)-4-(4,4-Difluorocyclohexyl)-2-[1-(5-{[(4S)-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 26, in 2 ml of methanol, 0.5 ml of 2 N hydrochloric acid was added, and the mixture was stirred at 50° C. for 3 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 added, 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 101.2 mg of the title compound as a white solid (yield: 99%).

Workup

  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

Sources & evidence

ORD record
ord-c1cfc3fe80bb45dd9d816b68fae34c40
Source dataset
uspto-grants-2016_04
Patent number
US09321747B2

Reaction notes

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