Hydrochloric Acid → (5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-2-(1-{5-[3-hydroxy-2-(hydroxymethyl)propoxy]pyrimidin-2-yl}piperidin-4-yl)-7,7-dimethyl-5,6,7,8-tetrahydr oquinolin-5-ol dihydrochloride

HRID 632580Notes

Reaction equation

HRID 632580 reaction equation
[F:1][C:2]1([F:52])[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][CH:35]([CH2:38][OH:39])[CH2:36][OH:37])=[CH:29][N:28]=4)[CH2:23][CH2:22]3)[C:9]=2[C@@H:40]([F:51])[C:41]2[CH:46]=[CH:45][C:44]([C:47]([F:50])([F:49])[F:48])=[CH:43][CH:42]=2)[CH2:4][CH2:3]1.[ClH:53]>C(OCC)(=O)C>[ClH:53].[ClH:53].[F:52][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][CH:35]([CH2:38][OH:39])[CH2:36][OH:37])=[CH:29][N:28]=4)[CH2:23][CH2:22]3)[C:9]=2[C@@H:40]([F:51])[C:41]2[CH:46]=[CH:45][C:44]([C:47]([F:48])([F:50])[F:49])=[CH:43][CH:42]=2)[CH2:6][CH2:7]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 71656703(5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-2-(1-{5-[3-hydroxy-2-(hydroxymethyl)propoxy]pyrimidin-2-yl}piperidin-4-yl)-7,7-dimethyl-5,6,7,8-tetrahydr oquinolin-5-ol

Product 1

HCID 71656702(5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-2-(1-{5-[3-hydroxy-2-(hydroxymethyl)propoxy]pyrimidin-2-yl}piperidin-4-yl)-7,7-dimethyl-5,6,7,8-tetrahydr oquinolin-5-ol dihydrochlorideYield 86%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 0.70 g (0.95 mmol) of (5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-2-(1-{5-[3-hydroxy-2-(hydroxymethyl)propoxy]pyrimidin-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 Reference Example 22, in 4.8 ml of ethyl acetate, 0.17 ml (2.0 mmol) of 35% hydrochloric acid was added dropwise with stirring at 60° C. Then, the reaction mixture was cooled to 20° C. and stirred for 3 hours. The precipitated solid was obtained by filtration, washed with 5 ml of ethyl acetate twice and then dried under reduced pressure at 60° C. to provide 659 mg of the title compound as a white powder (yield: 86%).

Workup

  1. temperatureThen, the reaction mixture was cooled to 20° C.
  2. stirringstirred for 3 hours
  3. customThe precipitated solid was obtained by filtration
  4. washwashed with 5 ml of ethyl acetate twice
  5. customdried under reduced pressure at 60° C.

Sources & evidence

ORD record
ord-ae51212294cd40648f31b0fffa767302
Source dataset
uspto-grants-2016_04
Patent number
US09321747B2

Reaction notes

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