Triethyl phosphonoacetate → ethyl (2E,4E)-5-[3-cyano-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl]penta-2,4-dienoate

HRID 1986500Notes

Reaction equation

HRID 1986500 reaction equation
C(OP([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])(OCC)=O)C.[H-].[Na+].[CH2:17]([C:21]1[C:30]([C:31]#[N:32])=[C:29]([C:33]2[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=2)[C:28]2[C:23](=[CH:24][CH:25]=[C:26](/[CH:40]=[CH:41]/[CH:42]=O)[CH:27]=2)[N:22]=1)[CH:18]([CH3:20])[CH3:19]>O1CCCC1.C(OCC)(=O)C>[C:31]([C:30]1[C:21]([CH2:17][CH:18]([CH3:20])[CH3:19])=[N:22][C:23]2[C:28]([C:29]=1[C:33]1[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=1)=[CH:27][C:26](/[CH:40]=[CH:41]/[CH:42]=[CH:9]/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:25][CH:24]=2)#[N:32]

Participants

6

Reactant 3

HCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 51050345HCID 51050345, compound

Product 1

HCID 51050347ethyl (2E,4E)-5-[3-cyano-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl]penta-2,4-dienoateYield 75.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of ethyl diethylphosphonoacetate (1.90 g, 10.2 mmol) in tetrahydrofuran (50 ml) was added sodium hydride (60% in oil, 408 mg, 10.2 mmol) at 0° C. and the mixture was stirred for 10 min. To the reaction mixture was added 2-isobutyl-4-(4-methylphenyl)-6-[(1E)-3-oxoprop-1-en-1-yl]quinoline-3-carbonitrile (3.00 g, 8.47 mmol). The temperature of the mixture was raised to room temperature and the mixture was stirred for 10 min. The reaction mixture was diluted with a mixture of tetrahydrofuran and ethyl acetate, washed successively with 2N aqueous sodium hydroxide solution, 1N hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give yellow crystals. The crystals were washed with diisopropyl ether to give ethyl (2E,4E)-5-[3-cyano-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl]penta-2,4-dienoate (2.71 g, yield 75%) as yellow crystals. The solvent of the mother liquor was removed under reduced pressure and the residue was purified by silica gel column chromatography to give ethyl (2E,4E)-5-[3-cyano-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl]penta-2,4-dienoate (320 mg, yield 9%) as yellow crystals.

Workup

  1. stirringthe mixture was stirred for 10 min
  2. washwashed successively with 2N aqueous sodium hydroxide solution, 1N hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customto give yellow crystals
  6. washThe crystals were washed with diisopropyl ether

Sources & evidence

ORD record
ord-847c04a94bca4ecfab25913cc3bc3e59
Source dataset
uspto-grants-2009_06
Patent number
US07547710B2

Reaction notes

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