Hydrogen Bromide → (5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-2-(1-{5-[3-hydroxy-2-(hydroxymethyl)-2-methylpropoxy]pyrimidin-2-yl}piperidin-4-yl)-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol dihydrobromide

HRID 632582Notes

Reaction equation

HRID 632582 reaction equation
[F:1][C:2]1([F:53])[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:35]([CH2:39][OH:40])([CH3:38])[CH2:36][OH:37])=[CH:29][N:28]=4)[CH2:23][CH2:22]3)[C:9]=2[C@@H:41]([F:52])[C:42]2[CH:47]=[CH:46][C:45]([C:48]([F:51])([F:50])[F:49])=[CH:44][CH:43]=2)[CH2:4][CH2:3]1.[BrH:54]>C(C(C)=O)C>[BrH:54].[BrH:54].[F:53][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:35]([CH2:39][OH:40])([CH3:38])[CH2:36][OH:37])=[CH:29][N:28]=4)[CH2:23][CH2:22]3)[C:9]=2[C@@H:41]([F:52])[C:42]2[CH:47]=[CH:46][C:45]([C:48]([F:49])([F:51])[F:50])=[CH:44][CH:43]=2)[CH2:6][CH2:7]1

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 71656789(5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-2-(1-{5-[3-hydroxy-2-(hydroxymethyl)-2-methylpropoxy]pyrimidin-2-yl}piperidin-4-yl)-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol

Product 1

HCID 71656788(5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-2-(1-{5-[3-hydroxy-2-(hydroxymethyl)-2-methylpropoxy]pyrimidin-2-yl}piperidin-4-yl)-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol dihydrobromideYield 96.1%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 50.7 mg (0.0675 mmol) of (5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-2-(1-{5-[3-hydroxy-2-(hydroxymethyl)-2-methylpropoxy]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 19, in 0.5 ml of methyl ethyl ketone, 15 μl (0.13 mmol) of 47% hydrobromic acid was added dropwise with stirring at 40° C. Then, the reaction mixture was cooled to 20° C. and stirred for 30 minutes. The precipitated solid was obtained by filtration, washed with methyl ethyl ketone and then dried under reduced pressure at 60° C. to provide 57 mg of the title compound as a white powder (yield: 93%).

Workup

  1. temperatureThen, the reaction mixture was cooled to 20° C.
  2. stirringstirred for 30 minutes
  3. customThe precipitated solid was obtained by filtration
  4. washwashed with methyl ethyl ketone
  5. customdried under reduced pressure at 60° C.

Sources & evidence

ORD record
ord-3ad66ed29b374df6b2b800843c0288d5
Source dataset
uspto-grants-2016_04
Patent number
US09321747B2

Reaction notes

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