Tetrahydrofuran → HCID 58636785, compound

HRID 1158975Notes

Reaction equation

HRID 1158975 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:38])[N:9]([CH2:18][C:19]1[CH:20]=[N:21][C:22]([CH3:37])=[C:23]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]#[N:36])[CH:30]=2)[C:24]=1C=O)[C:10]1[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][CH:11]=1)([CH3:6])([CH3:5])[CH3:4].C(=O)(O)[O-:40].[Na+].[O:44]1[CH2:48][CH2:47][CH2:46][CH2:45]1>>[CH3:45][O:44][C:48](=[O:40])/[CH:47]=[CH:46]/[C:24]1[C:19]([CH2:18][N:9]([C:8]([O:7][C:3]([CH3:6])([CH3:5])[CH3:4])=[O:38])[C:10]2[CH:11]=[CH:12][C:13]([C:16]#[N:17])=[CH:14][CH:15]=2)=[CH:20][N:21]=[C:22]([CH3:37])[C:23]=1[O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]#[N:36])[CH:30]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 58636705HCID 58636705, compound

Product 1

HCID 58636785HCID 58636785, compoundYield 738%

Procedure

To a solution of sodium hydride (124 mg, 60% in oil, 3.1 mmol) in anhydrous tetrahydrofuran (10 mL) was added methyl diethyl phosphonoacetate (661 mg, 3.1 mmol) at −78° C. under nitrogen atmosphere and stirred for 15 minutes. To the reaction mixture was added 5-(3-cyano-benzyloxy)-4-formyl-6-methyl-pyridin-3-ylmethyl]-(4-cyano-phenyl)-carbamic acid tert-butyl ester (109) (523 mg, 1.1 mmol) and stirred for 15 minutes. The reaction mixture was then poured into a cold solution of saturated aqueous sodium bicarbonate, and the crude product extracted with dichloromethane, dried over anhydrous magnesium sulfate. Evaporation of the solvent gave a crude residue, which was purified by column chromatography on silica gel using a gradient mixture of ethyl acetate:hexane (0:1 to 1:1) as an eluant to give (E)-3-[5-{[tert-butoxycarbonyl-(4-cyano-phenyl)-amino]-methyl}-3-(3-cyano-benzyloxy)-2-methyl-pyridin-4-yl]-acrylic acid methyl ester (120) (428 mg, 738% yield) as a colorless oil.

Workup

  1. stirringstirred for 15 minutes
  2. extractionthe crude product extracted with dichloromethane
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customEvaporation of the solvent
  5. customgave a crude residue, which
  6. customwas purified by column chromatography on silica gel using
  7. additiona gradient mixture of ethyl acetate:hexane (0:1 to 1:1) as an eluant

Sources & evidence

ORD record
ord-85fc33fd8bb9461abc90cbc9e779455d
Source dataset
uspto-grants-2010_10
Patent number
US07812037B2

Reaction notes

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