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

HRID 715855Notes

Reaction equation

HRID 715855 reaction equation
[F:1][C:2]1([F:46])[CH2:7][CH2:6][CH:5]([C:8]2[C:17]3[CH: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]([OH:33])=[CH:29][N:28]=4)[CH2:23][CH2:22]3)[C:9]=2[CH:34]([F:45])[C:35]2[CH:40]=[CH:39][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:37][CH:36]=2)[CH2:4][CH2:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:53](I)[CH3:54].O>CN(C)C=O>[F:46][C:2]1([F:1])[CH2:3][CH2:4][CH:5]([C:8]2[C:17]3[CH:16]([OH:18])[CH2:15][C:14]([CH3:19])([CH3:20])[CH2:13][C:12]=3[N:11]=[C:10]([CH:21]3[CH2:22][CH2:23][N:24]([C:27]4[N:32]=[CH:31][C:30]([O:33][CH2:53][CH3:54])=[CH:29][N:28]=4)[CH2:25][CH2:26]3)[C:9]=2[CH:34]([F:45])[C:35]2[CH:36]=[CH:37][C:38]([C:41]([F:43])([F:42])[F:44])=[CH:39][CH:40]=2)[CH2:6][CH2:7]1

Participants

6

Reactant 4

HCID 962WaterHCID 6340IodoethaneHCID 10796Cesium carbonateHCID 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 763723624-(4,4-Difluorocyclohexyl)-2-[1-(5-ethoxypyrimidine-2-yl)piperidin-4-yl]-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-olYield 86.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 50 mg (0.077 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, in 1.0 ml of N,N-dimethylformamide, 75 mg (0.23 mmol) of cesium carbonate and 12 μl (0.15 mmol) of ethyl iodide were added, and the reaction solution was stirred at room temperature for 1 hour. After completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and dried with anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by preparative thin layer chromatography [n-hexane/ethyl acetate=70/30 (V/V)] to provide 45 mg of the title compound as a white solid (yield: 85%).

Workup

  1. customAfter completion of the reaction
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated sodium chloride aqueous solution
  4. dry with materialdried with anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe obtained residue was purified by preparative thin layer chromatography [n-hexane/ethyl acetate=70/30 (V/V)]

Sources & evidence

ORD record
ord-6a1a1fc53cc849548b37e8a0972597b3
Source dataset
uspto-grants-2015_11
Patent number
US09187450B2

Reaction notes

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