Acetone → (5S)-4-(4,4-Difluorocyclohexyl)-2-[1-(5-{[(2S)-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 dihydrobromide

HRID 632594Notes

Reaction equation

HRID 632594 reaction equation
[BrH:1].CC(C)=O.[F:6][C:7]1([F:56])[CH2:12][CH2:11][CH:10]([C:13]2[C:22]3[C@@H:21]([OH:23])[CH2:20][C:19]([CH3:25])([CH3:24])[CH2:18][C:17]=3[N:16]=[C:15]([CH:26]3[CH2:31][CH2:30][N:29]([C:32]4[N:37]=[CH:36][C:35]([O:38][CH2:39][C@@H:40]([OH:43])[CH2:41][OH:42])=[CH:34][N:33]=4)[CH2:28][CH2:27]3)[C:14]=2[C@@H:44]([F:55])[C:45]2[CH:50]=[CH:49][C:48]([C:51]([F:54])([F:53])[F:52])=[CH:47][CH:46]=2)[CH2:9][CH2:8]1>COC(C)(C)C>[BrH:1].[BrH:1].[F:56][C:7]1([F:6])[CH2:8][CH2:9][CH:10]([C:13]2[C:22]3[C@@H:21]([OH:23])[CH2:20][C:19]([CH3:24])([CH3:25])[CH2:18][C:17]=3[N:16]=[C:15]([CH:26]3[CH2:31][CH2:30][N:29]([C:32]4[N:37]=[CH:36][C:35]([O:38][CH2:39][C@@H:40]([OH:43])[CH2:41][OH:42])=[CH:34][N:33]=4)[CH2:28][CH2:27]3)[C:14]=2[C@@H:44]([F:55])[C:45]2[CH:50]=[CH:49][C:48]([C:51]([F:52])([F:54])[F:53])=[CH:47][CH:46]=2)[CH2:11][CH2:12]1

Participants

5

Reactant 3

HCID 180AcetoneHCID 260Hydrogen BromideHCID 71657166HCID 71657166, compound

Product 1

HCID 71657167(5S)-4-(4,4-Difluorocyclohexyl)-2-[1-(5-{[(2S)-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 dihydrobromideYield 75.3%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

Reactions similar to those of Example 13 were performed except for using 13.0 μl (114 μmol) of 47% hydrobromic acid instead of 35% hydrochloric acid and using 0.37 ml of a 1:1 mixed solvent of acetone and tert-butyl methyl ether instead of acetone, and from 37.0 mg (51.2 μmol) of (5S)-4-(4,4-Difluorocyclohexyl)-2-[1-(5-{[(2S)-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, which was prepared by a method similar to that of Reference Example 25, 34.1 mg of the title compound was obtained as a white powder (yield: 75%).

Sources & evidence

ORD record
ord-eb5d12897a11495a98b6c159221bf220
Source dataset
uspto-grants-2016_04
Patent number
US09321747B2

Reaction notes

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