tert-Butanol → HCID 86682424, compound

HRID 715896Notes

Reaction equation

HRID 715896 reaction equation
[F:1][C:2]1([F:48])[CH2:7][CH2:6][CH:5]([C:8]2[C:17]3[CH:16]([O:18][CH2:19][C:20]4[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=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][NH:33][CH2:32][CH2:31]3)[C:9]=2[CH:36]([F:47])[C:37]2[CH:42]=[CH:41][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:39][CH:38]=2)[CH2:4][CH2:3]1.Br[C:50]1[N:55]=[CH:54][CH:53]=[CH:52][N:51]=1.C(N(C(C)C)CC)(C)C.C(O)(C)(C)C>O>[F:48][C:2]1([F:1])[CH2:7][CH2:6][CH:5]([C:8]2[C:17]3[CH:16]([O:18][CH2:19][C:20]4[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=4)[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:50]4[N:55]=[CH:54][CH:53]=[CH:52][N:51]=4)[CH2:32][CH2:31]3)[C:9]=2[CH:36]([F:47])[C:37]2[CH:38]=[CH:39][C:40]([C:43]([F:45])([F:46])[F:44])=[CH:41][CH:42]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 783452-BromopyrimidineHCID 81531DiisopropylethylamineHCID 86682426(-)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-2-(piperidin-4-yl)-5,6,7,8-tetrahydroquinoline

Product 1

HCID 86682424HCID 86682424, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
65 °C

Procedure

To 1.21 g (1.79 mmol) of (−)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-2-(piperidin-4-yl)-5,6,7,8-tetrahydroquinoline, which was prepared by a method similar to that of Reference Example 10, 0.90 g (5.7 mmol) of 2-bromopyrimidine, 1.0 ml (5.9 mmol) of diisopropylethylamine and 20 ml of tert-butanol were added, and the reaction solution was stirred at 65° C. for 2.5 hours. 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. n-Hexane was added to the obtained residue and the precipitate was obtained by filtration to provide 1.17 g of the title compound as a white solid (yield: 87%).

Workup

  1. additionwere added
  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. additionn-Hexane was added to the obtained residue
  8. customthe precipitate was obtained by filtration

Sources & evidence

ORD record
ord-2ae7482843c44512a98db353f2aed498
Source dataset
uspto-grants-2015_11
Patent number
US09187450B2

Reaction notes

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