Acetic Acid → 2-(Pyridin-4-yl)-1-(4-(quinolin-2-ylmethoxy)phenyl)ethan-1-one

HRID 33822

反応式

HRID 33822 の反応式
C([N-]C(C)C)(C)C.[Li+].[N:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=1.CON(C)[C:19](=[O:38])[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]2[CH:37]=[CH:36][C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:29]=2)=[CH:22][CH:21]=1.C(O)(=O)C>O1CCCC1>[N:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:19]([C:20]2[CH:21]=[CH:22][C:23]([O:26][CH2:27][C:28]3[CH:37]=[CH:36][C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[N:29]=3)=[CH:24][CH:25]=2)=[O:38])=[CH:11][CH:10]=1

参加物

6

反応物 4

HCID 176Acetic AcidHCID 79634-Methylpyridine3 回HCID 2724682Lithium diisopropylamideHCID 44234674Benzamide, N-methoxy-N-methyl-4-(2-quinolinylmethoxy)-

生成物 1

HCID 336797272-(Pyridin-4-yl)-1-(4-(quinolin-2-ylmethoxy)phenyl)ethan-1-one収率 80%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

To a solution of Lithium diisopropyl amide (1.0M) in tetrahydrofuran was added 4-picoline dropwise (7.55 ml, 5 eq.) at 0° C. under N2. After 30 min the anion was cooled to −78° C. In a separate round bottom flask N-Methoxy-N-methyl-4-(quinolin-2-ylmethoxy)-benzamide (5.0, 15.5 mmole) was dissolved in tetrahydrofuran (77 ml, 0.2M) and cooled to −78° C. under N2. 1.2 eq. of the 4-picoline anion was added dropwise to the amide solution. After 45 min, 1 eq. more of the 4-picoline anion was added. After an addition 30 min, acetic acid (40 ml) was added dropwise and the reaction was slowly warmed to ambient temperature. The solid product (acetate salt) was filtered and partitioned between saturated sodium bicarbonate and dichloromethane. The layers were separated, dried magnesium sulfate filtered and concentrated to provide the title compound as a tan solid (4.41 g, 80%). 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J=5.8 Hz, 2 H), 8.19 (d, J=8.7 Hz, 1 H), 8.07 (d, J=8.7 Hz, 1H), 7.93 (m, 2 H), 7.82 (d, J=8.3 Hz, 1 H), 7.75 (m, 1 H), 7.61 (d, J=8.3 Hz, 1 H), 7.54 (dt, J=7.9, 1.0 Hz, 1 H), 7.23 (m, 2 H) 7.07 (m, 2H), 5.42 (s, 2H), 4.19 (s, 2H); MS: (M+H m/z=355.2).

後処理

  1. temperaturecooled to −78° C. under N2
  2. additionwas added dropwise
  3. temperaturethe reaction was slowly warmed to ambient temperature
  4. filtrationThe solid product (acetate salt) was filtered
  5. custompartitioned between saturated sodium bicarbonate and dichloromethane
  6. customThe layers were separated
  7. filtrationdried magnesium sulfate filtered
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-fa627596c921474d9295989408bf324f
出典データセット
uspto-grants-2008_09
特許番号
US07429665B2

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