Diethyl (ethoxymethylene)malonate → 2,3-Difluoro-6-(2,2-diethoxycarbonylethenyl)amino-[(2-hydroxypropyl)oxy]benzene

HRID 846328Notes

Reaction equation

HRID 846328 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([NH2:9])[C:3]=1[O:10][CH2:11][CH:12]([O:14]C1CCCCO1)[CH3:13].C(O[CH:24]=[C:25]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:26]([O:28][CH2:29][CH3:30])=[O:27])C>>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([NH:9][CH:24]=[C:25]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:3]=1[O:10][CH2:11][CH:12]([OH:14])[CH3:13]

Participants

3

Reactant 2

HCID 6871Diethyl (ethoxymethylene)malonateHCID 146971812,3-Difluoro-6-amino-{[2-(tetrahydropyran-2-yl)oxypropyl]oxy}benzene

Product 1

HCID 146971832,3-Difluoro-6-(2,2-diethoxycarbonylethenyl)amino-[(2-hydroxypropyl)oxy]benzene

Procedure

To the total amount of the product obtained in Example 2 was added 1.24 g of diethyl ethoxymethylenemalonate (XVI, Y=EtO, alkyl=Et, hereinafter abbreviated as EMME). The mixture was heated to 145° to 150° C. with stirring. After 1.5 hours, the system was evacuated to remove formed ethanol, and the mixture was heated a further 30 minutes with stirring under reduced pressure. After cooling, the product was isolated through silica gel column chromatography to yield 1.33 g of the titled compound, which has no tetrahydropyranyl moiety.

Workup

  1. temperatureThe mixture was heated to 145° to 150° C.
  2. customthe system was evacuated
  3. customto remove
  4. customformed ethanol
  5. temperaturethe mixture was heated a further 30 minutes
  6. stirringwith stirring under reduced pressure
  7. temperatureAfter cooling
  8. customthe product was isolated through silica gel column chromatography

Sources & evidence

ORD record
ord-4d4d047b26c846da8584446649c91fc3
Source dataset
uspto-grants-1992_08
Patent number
US05136059

Reaction notes

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