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

HRID 33822

Reaction equation

HRID 33822 reaction equation
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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-fa627596c921474d9295989408bf324f
Source dataset
uspto-grants-2008_09
Patent number
US07429665B2

Linked notes

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