Ethyl bromoacetate → HCID 86682461, compound

HRID 715880Notes

Reaction equation

Br[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[F:8][C:9]1([F:53])[CH2:14][CH2:13][CH:12]([C:15]2[C:24]3[CH: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]([OH:40])=[CH:36][N:35]=4)[CH2:30][CH2:29]3)[C:16]=2[CH: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)[CH2:11][CH2:10]1>>[F:53][C:9]1([F:8])[CH2:10][CH2:11][CH:12]([C:15]2[C:24]3[CH:23]([OH:25])[CH2:22][C:21]([CH3:26])([CH3:27])[CH2:20][C:19]=3[N:18]=[C:17]([CH:28]3[CH2:29][CH2:30][N:31]([C:34]4[N:39]=[CH:38][C:37]([O:40][CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4])=[CH:36][N:35]=4)[CH2:32][CH2:33]3)[C:16]=2[CH:41]([F:52])[C:42]2[CH:43]=[CH:44][C:45]([C:48]([F:49])([F:51])[F:50])=[CH:46][CH:47]=2)[CH2:13][CH2:14]1

Participants

Reactant 2

HCID 7748Ethyl bromoacetate

HCID 76372263(-)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-2-[1-(5-hydroxypyrimidin-2-yl)piperidin-4-yl]-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol

Product 1

HCID 86682461HCID 86682461, compound

Procedure

Reactions similar to those of Example 13 were performed except for using ethyl bromoacetate instead of ethyl iodide, and from 82 mg (0.13 mmol) of (−)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-2-[1-(5-hydroxypyrimidin-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 Example 4, 61 mg of 4-(4,4-Difluorocyclohexyl)-2-{1-[5-(2-ethoxy-2-oxoethoxy)pyrimidin-2-yl]piperidin-4-yl}-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol was obtained. To a solution of 61 mg (0.083 mmol) of 4-(4,4-Difluorocyclohexyl)-2-{1-[5-(2-ethoxy-2-oxoethoxy)pyrimidin-2-yl]piperidin-4-yl}-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol obtained above in 5 ml of diethyl ether, 0.30 ml (0.33 mmol) of 1.1 N methyl magnesium bromide-diethyl ether solution was added at 0° C. The temperature of the reaction solution was raised to room temperature and the reaction solution was stirred for 1 hour. After completion of the reaction, an ammonium chloride aqueous solution was poured into the reaction solution and the reaction solution was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and dried with anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by thin layer silica gel chromatography [n-hexane/ethyl acetate=5/6 (V/V)] to provide 18 mg of the title compound as a white solid (yield: 30%).

Sources & evidence

ORD record: ord-791f058740af4049bbf1ef32f4ec678b
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187450B2

Reaction notes

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