Hydrochloric Acid → (-)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-2-(1-{5-[(1E)-3-methylbut-1-ene-1-yl]pyrimidin-2-yl}piperidin-4-yl)-5,6,7,8-tetrahydroquinolin-5-ol

HRID 715873ノート

反応式

HRID 715873 の反応式
[F:1][C:2]1([F:60])[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)[CH2:43][CH:44]([CH3:46])[CH3:45])=[CH:38][N:37]=4)[CH2:32][CH2:31]3)[C:9]=2[CH:48]([F:59])[C:49]2[CH:54]=[CH:53][C:52]([C:55]([F:58])([F:57])[F:56])=[CH:51][CH:50]=2)[CH2:4][CH2:3]1.Cl.C(=O)([O-])O.[Na+]>O1CCOCC1>[F:60][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[CH2:31][CH2:32][N:33]([C:36]4[N:41]=[CH:40][C:39](/[CH:42]=[CH:43]/[CH:44]([CH3:45])[CH3:46])=[CH:38][N:37]=4)[CH2:34][CH2:35]3)[C:9]=2[CH:48]([F:59])[C:49]2[CH:50]=[CH:51][C:52]([C:55]([F:56])([F:58])[F:57])=[CH:53][CH:54]=2)[CH2:6][CH2:7]1

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 86682448HCID 86682448、化合物

生成物 1

HCID 86682447(-)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-2-(1-{5-[(1E)-3-methylbut-1-ene-1-yl]pyrimidin-2-yl}piperidin-4-yl)-5,6,7,8-tetrahydroquinolin-5-ol収率 73%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a solution of 118 mg (0.141 mmol) of 4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-2-{1-[5-(1-hydroxy-3-methylbutyl)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 27, in 2 ml of 1,4-dioxane, 2 ml of 2 N hydrochloric acid was added, and the reaction solution was stirred at 100° C. for 3.5 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=92/8-88/12 (V/V)] and the fraction including the desired compound was concentrated under reduced pressure to provide 72 mg of the title compound as a white solid (yield: 73%).

後処理

  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

出典と根拠

ORDレコード
ord-1ddf966d83ad45279fed2fb6814e6af2
出典データセット
uspto-grants-2015_11
特許番号
US09187450B2

反応ノート

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