Trifluoroacetic acid → HCID 76372517, compound

HRID 715865Notes

Reaction equation

HRID 715865 reaction equation
[F:1][C:2]1([F:59])[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]([CH:42](O)[CH:43]([CH3:45])[CH3:44])=[CH:38][N:37]=4)[CH2:32][CH2:31]3)[C:9]=2[CH:47]([F:58])[C:48]2[CH:53]=[CH:52][C:51]([C:54]([F:57])([F:56])[F:55])=[CH:50][CH:49]=2)[CH2:4][CH2:3]1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+]>ClCCl>[F:59][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]([CH3:29])([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][CH:43]([CH3:44])[CH3:45])=[CH:38][N:37]=4)[CH2:32][CH2:31]3)[C:9]=2[CH:47]([F:58])[C:48]2[CH:49]=[CH:50][C:51]([C:54]([F:55])([F:57])[F:56])=[CH:52][CH:53]=2)[CH2:6][CH2:7]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 516892Sodium BicarbonateHCID 866824344-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-2-{1-[5-(1-hydroxy-2-methylpropyl)pyrimidin-2-yl]piperidin-4-yl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline

Product 1

HCID 76372517HCID 76372517, compoundYield 27.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 70 mg (0.085 mmol) of 4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-2-{1-[5-(1-hydroxy-2-methylpropyl)pyrimidin-2-yl]piperidin-4-yl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline, which was prepared by a method similar to that of Reference Example 19, in 5 ml of dichloromethane, 2 ml of triethyl silane and 1 ml of trifluoroacetic acid were added, and the reaction solution was stirred at room temperature for 41 hours. 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=95/5-85/15 (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 16 mg of the title compound as a white solid (yield: 27%).

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. concentrationwas concentrated under reduced pressure
  7. additionn-Hexane was added to the obtained residue
  8. customthe precipitate was obtained by filtration

Sources & evidence

ORD record
ord-56724d73e83d411fb03a1ea5fc738f26
Source dataset
uspto-grants-2015_11
Patent number
US09187450B2

Reaction notes

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