Hydrochloric Acid → HCID 76372215、化合物

HRID 715846ノート

反応式

HRID 715846 の反応式
[F:1][C:2]1([F:48])[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][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.Cl[C:50]1[N:55]=[CH:54][C:53]([O:56][CH3:57])=[CH:52][N:51]=1.Cl.C(=O)([O-])O.[Na+]>O1CCOCC1>[F:1][C:2]1([F:48])[CH2:7][CH2:6][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:50]4[N:55]=[CH:54][C:53]([O:56][CH3:57])=[CH:52][N:51]=4)[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

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 5890582-Chloro-5-methoxypyrimidineHCID 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

生成物 1

HCID 76372215HCID 76372215、化合物収率 45%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

To 100 mg (0.15 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, 64 mg (0.44 mmol) of 2-chloro-5-methoxypyrimidine and 1 ml of 1,4-dioxane were added, and the reaction solution was stirred at 80° C. for 26.6 hours. After completion of the reaction, 0.5 ml of 6 N hydrochloric acid was added to the reaction solution and the mixture was stirred at 50° C. for 8 hours. After completion of the reaction, saturated sodium hydrogencarbonate aqueous solution was added to the reaction mixture and the reaction mixture was 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=4/1 (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 44 mg of the title compound as a white powder (yield: 45%).

後処理

  1. additionwere added
  2. additionwas added to the reaction solution
  3. stirringthe mixture was stirred at 50° C. for 8 hours
  4. additionwas added to the reaction mixture
  5. extractionthe reaction mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with saturated sodium chloride aqueous solution
  7. dry with materialdried with anhydrous magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. concentrationwas concentrated under reduced pressure
  10. additionn-Hexane was added to the obtained residue
  11. customthe precipitate was obtained by filtration

出典と根拠

ORDレコード
ord-74189dc7b5554e75a1607f7220ecb473
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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