Sodium Bicarbonate → 4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-2-[1-(5-formylpyrimidin-2-yl)piperidin-4-yl]-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline

HRID 715897노트

반응식

HRID 715897 반응식
[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.Cl[C:50]1[N:55]=[CH:54][C:53]([CH:56]=[O:57])=[CH:52][N:51]=1.C1(C2CCCCCCCCCC=2)CCCCCCCCNN=1.C(=O)([O-])O.[Na+]>CN1CCCC1=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][C:53]([CH:56]=[O:57])=[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

참가 물질

6

반응물 4

HCID 516892Sodium BicarbonateHCID 216983502-Chloropyrimidine-5-carbaldehyde3회HCID 536302743-(Cycloundecen-1-yl)-1,2-diazacycloundec-2-eneHCID 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

생성물 1

HCID 866824324-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-2-[1-(5-formylpyrimidin-2-yl)piperidin-4-yl]-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline수율 87%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

To a solution of 1.00 g (1.48 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, in 5 ml of 1-methyl-2-pyrrolidone, 0.23 g (1.6 mmol) of 2-chloro-5-formyl pyrimidine and 265 μl (1.78 mmol) of diazabicycloundecene were added, and the reaction solution was stirred at room temperature for 1 hour. Then, 0.023 g (0.16 mmol) of 2-chloro-5-formyl pyrimidine was added thereto and the reaction solution was further stirred at room temperature for 0.58 hours. Furthermore, 0.023 g (0.16 mmol) of 2-chloro-5-formyl pyrimidine was added thereto and the reaction solution was stirred at room temperature for 1.5 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=40/10 (V/V)] and the fraction including the desired compound was concentrated under reduced pressure to provide 1.00 g of the title compound as a light yellow solid (yield: 87%).

후처리

  1. stirringthe reaction solution was further stirred at room temperature for 0.58 hours
  2. stirringthe reaction solution was stirred at room temperature for 1.5 hours
  3. customAfter completion of the reaction
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with saturated sodium chloride aqueous solution
  6. dry with materialdried with anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. concentrationwas concentrated under reduced pressure

출처 및 근거

ORD 기록
ord-670960fc55584c79b59006b393e05fe8
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09187450B2

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