Methanesulfonic 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 methanesulfonate

HRID 632584Notes

Reaction equation

HRID 632584 reaction equation
[CH3:1][S:2]([OH:5])(=[O:4])=[O:3].[F:6][C:7]1([F:58])[CH2:12][CH2:11][CH:10]([C:13]2[C:22]3[C@@H:21](O)[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:40]([CH2:44][OH:45])([CH3:43])[CH2:41][OH:42])=[CH:34][N:33]=4)[CH2:28][CH2:27]3)[C:14]=2[C@@H:46]([F:57])[C:47]2[CH:52]=[CH:51][C:50]([C:53]([F:56])([F:55])[F:54])=[CH:49][CH:48]=2)[CH2:9][CH2:8]1>COC(C)(C)C>[CH3:1][S:2]([O:5][C@H:21]1[CH2:20][C:19]([CH3:24])([CH3:25])[CH2:18][C:17]2[N:16]=[C:15]([CH:26]3[CH2:27][CH2:28][N:29]([C:32]4[N:37]=[CH:36][C:35]([O:38][CH2:39][C:40]([CH2:41][OH:42])([CH3:43])[CH2:44][OH:45])=[CH:34][N:33]=4)[CH2:30][CH2:31]3)[C:14]([C@@H:46]([F:57])[C:47]3[CH:52]=[CH:51][C:50]([C:53]([F:55])([F:54])[F:56])=[CH:49][CH:48]=3)=[C:13]([CH:10]3[CH2:11][CH2:12][C:7]([F:6])([F:58])[CH2:8][CH2:9]3)[C:22]1=2)(=[O:4])=[O:3]

Participants

4

Reactant 2

HCID 6395Methanesulfonic AcidHCID 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 117687920(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 methanesulfonateYield 50.7%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

Reactions similar to those of Example 3 were performed except for using 4.5 μl (0.069 mmol) of methanesulfonic acid instead of 47% hydrobromic acid salt and using 2.5 ml of tert-butyl methyl ether instead of methyl ethyl ketone, and from 51.8 mg (0.069 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, 29 mg of the title compound was obtained as a white powder (yield: 50%).

Sources & evidence

ORD record
ord-73d68ebc811749c9af9a771e5a74684c
Source dataset
uspto-grants-2016_04
Patent number
US09321747B2

Reaction notes

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