Hydrochloric Acid → (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 dihydrochloride

HRID 632583Notes

Reaction equation

HRID 632583 reaction equation
[ClH:1].C(OCC)(=O)C.[F:8][C:9]1([F:60])[CH2:14][CH2:13][CH:12]([C:15]2[C:24]3[C@@H:23]([OH:25])[CH2:22][C:21]([CH3:27])([CH3:26])[CH2:20][C:19]=3[N:18]=[C:17]([CH:28]3[CH2:33][CH2:32][N:31]([C:34]4[N:39]=[CH:38][C:37]([O:40][CH2:41][C:42]([CH2:46][OH:47])([CH3:45])[CH2:43][OH:44])=[CH:36][N:35]=4)[CH2:30][CH2:29]3)[C:16]=2[C@@H:48]([F:59])[C:49]2[CH:54]=[CH:53][C:52]([C:55]([F:58])([F:57])[F:56])=[CH:51][CH:50]=2)[CH2:11][CH2:10]1>C(O)C>[ClH:1].[ClH:1].[F:60][C:9]1([F:8])[CH2:10][CH2:11][CH:12]([C:15]2[C:24]3[C@@H:23]([OH:25])[CH2:22][C:21]([CH3:26])([CH3:27])[CH2:20][C:19]=3[N:18]=[C:17]([CH:28]3[CH2:33][CH2:32][N:31]([C:34]4[N:39]=[CH:38][C:37]([O:40][CH2:41][C:42]([CH2:46][OH:47])([CH3:45])[CH2:43][OH:44])=[CH:36][N:35]=4)[CH2:30][CH2:29]3)[C:16]=2[C@@H:48]([F:59])[C:49]2[CH:54]=[CH:53][C:52]([C:55]([F:56])([F:58])[F:57])=[CH:51][CH:50]=2)[CH2:13][CH2:14]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 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 71656790(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 dihydrochlorideYield 76.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Reactions similar to those of Example 3 were performed except for using 12 μl (0.14 mmol) of 35% hydrochloric acid instead of 47% hydrobromic acid and using a mixed solution of 0.5 ml of ethyl acetate and 35 μl of ethanol instead of methyl ethyl ketone, and from 51.2 mg (0.0682 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, 43 mg of the title compound was obtained as a white powder (yield: 77%).

Sources & evidence

ORD record
ord-20a0f9ca780447c4a97adc0394ea02d4
Source dataset
uspto-grants-2016_04
Patent number
US09321747B2

Reaction notes

Loading…