Sodium hydride → Isopropyl 2-chloro-4-fluoro-5-{3-[2-(ethoxycarbonyl)-2-fluoro-1-fluoromethyl-vinyl]ureido}-benzoate

HRID 845923Notes

Reaction equation

HRID 845923 reaction equation
[NH2:1]/[C:2](/[CH2:10][F:11])=[C:3](/[F:9])\[C:4]([O:6][CH2:7][CH3:8])=[O:5].[H-].[Na+].[Cl:14][C:15]1[CH:26]=[C:25]([F:27])[C:24]([N:28]=[C:29]=[O:30])=[CH:23][C:16]=1[C:17]([O:19][CH:20]([CH3:22])[CH3:21])=[O:18]>CN(C)C=O>[Cl:14][C:15]1[CH:26]=[C:25]([F:27])[C:24]([NH:28][C:29]([NH:1][C:2]([CH2:10][F:11])=[C:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])[F:9])=[O:30])=[CH:23][C:16]=1[C:17]([O:19][CH:20]([CH3:21])[CH3:22])=[O:18]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 13519895Isopropyl 2-chloro-4-fluoro-5-isocyanatobenzoateHCID 86742181Ethyl 3-amino-2,4-difluorocrotonate

Product 1

HCID 70411567Isopropyl 2-chloro-4-fluoro-5-{3-[2-(ethoxycarbonyl)-2-fluoro-1-fluoromethyl-vinyl]ureido}-benzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 1.80 g of ethyl 3-amino-2,4-difluorocrotonate in 20 ml of absolute dimethylformamide is added dropwise with stirring during 10 minutes to 0.48 g of a 55% sodium hydride dispersion in 25 ml of dimethylformamide at room temperature, and the mixture is stirred for a further 15 minutes. Thereafter 2.81 g of isopropyl 2-chloro-4-fluoro-5-isocyanatobenzoate are added, with the result that the temperature of the reaction mixture rises to 35° C. Then the mixture is stirred for a further two hours at room temperature. The isopropyl 2-chloro-4-fluoro-5-{3-[2-(ethoxycarbonyl)-2-fluoro-1-fluoromethyl-vinyl]ureido}-benzoate formed as an intermediate is not isolated.

Workup

  1. customwith the result that the temperature of the reaction mixture
  2. customrises to 35° C
  3. stirringThen the mixture is stirred for a further two hours at room temperature

Sources & evidence

ORD record
ord-98452b8f0eb94a0b895a37c40bd7a870
Source dataset
uspto-grants-1988_07
Patent number
US04760163

Reaction notes

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