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

HRID 33822

반응식

HRID 33822 반응식
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

참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 79634-Methylpyridine3회HCID 2724682Lithium diisopropylamideHCID 44234674Benzamide, N-methoxy-N-methyl-4-(2-quinolinylmethoxy)-

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-fa627596c921474d9295989408bf324f
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07429665B2

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