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

HRID 715866Notes

Reaction equation

HRID 715866 reaction equation
[F:1][C:2]1([F:58])[CH2:7][CH2:6][CH:5]([C:8]2[C:17]3[CH:16]([O:18]CC4C=CC(OC)=CC=4)[CH2:15][C:14]([CH3:29])([CH3:28])[CH2:13][C:12]=3[N:11]=[C:10]([CH:30]3[CH2:35][CH2:34][N:33]([C:36]4[N:41]=[CH:40][C:39]([CH2:42][O:43][CH2:44][CH3:45])=[CH:38][N:37]=4)[CH2:32][CH2:31]3)[C:9]=2[CH: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)[CH2:4][CH2:3]1.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+]>ClCCl>[F:58][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]([CH3:28])([CH3:29])[CH2:13][C:12]=3[N:11]=[C:10]([CH:30]3[CH2:35][CH2:34][N:33]([C:36]4[N:41]=[CH:40][C:39]([CH2:42][O:43][CH2:44][CH3:45])=[CH:38][N:37]=4)[CH2:32][CH2:31]3)[C:9]=2[CH:46]([F:57])[C:47]2[CH:48]=[CH:49][C:50]([C:53]([F:54])([F:56])[F:55])=[CH:51][CH:52]=2)[CH2:6][CH2:7]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 7519AnisoleHCID 516892Sodium BicarbonateHCID 866824354-(4,4-Difluorocyclohexyl)-2-{1-[5-(ethoxymethyl)pyrimidin-2-yl]piperidin-4-yl}-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline

Product 1

HCID 76372519(-)-4-(4,4-Difluorocyclohexyl)-2-{1-[5-(ethoxymethyl)pyrimidin-2-yl]piperidin-4-yl}-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-olYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 68 mg (0.085 mmol) of 4-(4,4-Difluorocyclohexyl)-2-{1-[5-(ethoxymethyl)pyrimidin-2-yl]piperidin-4-yl}-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline, which was prepared by a method similar to that of Reference Example 21, in 1 ml of dichloromethane, 46 μl of anisole and 130 μl of trifluoroacetic acid were added, and the reaction solution was stirred at room temperature for 19 hours. Then, 100 μl of trifluoroacetic acid was further added and the reaction solution was stirred at room temperature for 1 hour. After completion of the reaction, the reaction solution was poured into saturated sodium hydrogencarbonate aqueous solution 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 subjected to silica gel column chromatography [n-hexane/ethyl acetate=98/2-70/30 (V/V)] and the fraction including the desired compound was concentrated under reduced pressure. n-Hexane was added to the obtained residue and the precipitate was obtained by filtration to provide 34 mg of the title compound as a white solid (yield: 58%).

Workup

  1. stirringthe reaction solution was stirred at room temperature for 1 hour
  2. customAfter completion of the reaction
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with saturated sodium chloride aqueous solution
  5. dry with materialdried with anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. concentrationwas concentrated under reduced pressure
  8. additionn-Hexane was added to the obtained residue
  9. customthe precipitate was obtained by filtration

Sources & evidence

ORD record
ord-95b9bfefcf7645a2b6bb94be79b7707b
Source dataset
uspto-grants-2015_11
Patent number
US09187450B2

Reaction notes

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