Aluminium lithium hydride → 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(4-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)acetamide

HRID 1050042노트

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HRID 1050042 반응식
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:29][C:30]3[CH:35]=[CH:34][C:33]([CH2:36][C:37]([CH3:44])([CH3:43])[C:38](OCC)=[O:39])=[C:32]([C:45]([F:48])([F:47])[F:46])[CH:31]=3)=[O:28])=[C:22]([F:49])[CH:21]=2)[CH:7]=[N:8][C:9]=1[O:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:29][C:30]3[CH:35]=[CH:34][C:33]([CH2:36][C:37]([CH3:44])([CH3:43])[CH2:38][OH:39])=[C:32]([C:45]([F:46])([F:48])[F:47])[CH:31]=3)=[O:28])=[C:22]([F:49])[CH:21]=2)[CH:7]=[N:8][C:9]=1[O:10][CH2:11][C:12]1[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=1)[CH3:2]

참가 물질

4

반응물 2

HCID 21226445Aluminium lithium hydrideHCID 90415745Ethyl 3-(4-(2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamido)-2-(trifluoromethyl)phenyl)-2,2-dimethylpropanoate

생성물 1

HCID 904180242-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(4-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)acetamide수율 82.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

To a mixture of ethyl 3-(4-(2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamido)-2-(trifluoromethyl)phenyl)-2,2-dimethylpropanoate (3.5 g, 5.13 mmol) in THF (200 mL) cooled to 0° C. was added LAH (0.389 g, 10.25 mmol) in portions. The mixture was stirred at 0° C. for 30 min. The mixture was quenched with 15% aqueous NaOH (10 mL). The mixture was dried over Na2SO4. The mixture was filtered and the filtrate was concentrated. The residue was purified by silica column chromatography (PE/EA=8:1). All fractions found to contain product by TLC (PE/EA=2:1, Rf=0.35) were combined and concentrated to yield a light yellow oil of 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(4-(3-hydroxy-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)acetamide (3 g, 4.21 mmol, 82.0% yield): 1H NMR (400 MHz, CD3OD) δ: 7.93 (d, J=2.0 Hz, 2H), 7.71 (d, J=8.4 Hz, 1H), 7.47-7.31 (m, 7H), 6.90 (d, J=8.4 Hz, 2H), 5.35 (s, 2H), 4.17-4.10 (m, 2H), 3.82-3.74 (m, 5H), 3.31-3.30 (m, 2H), 2.77 (s, 2H), 1.41 (t, J=6.8 Hz, 3H), 0.82 (s, 6H); ES-LCMS m/z 635 (M−120).

후처리

  1. customThe mixture was quenched with 15% aqueous NaOH (10 mL)
  2. dry with materialThe mixture was dried over Na2SO4
  3. filtrationThe mixture was filtered
  4. concentrationthe filtrate was concentrated
  5. customThe residue was purified by silica column chromatography (PE/EA=8:1)
  6. concentrationconcentrated

출처 및 근거

ORD 기록
ord-5188d60a1f49475891a9793050b55b03
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09382238B2

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