p-Toluenesulfonic acid monohydrate → Isopropyl 2-chloro-4-fluoro-5-{3-[2-(methoxycarbonyl)propenyl]ureido}-benzoate

HRID 845994Notes

Reaction equation

HRID 845994 reaction equation
[Cl:1][C:2]1[CH:13]=[C:12]([F:14])[C:11]([NH:15][C:16]([NH2:18])=[O:17])=[CH:10][C:3]=1[C:4]([O:6][CH:7]([CH3:9])[CH3:8])=[O:5].CO[CH:21]=[C:22]([CH3:27])[C:23]([O:25][CH3:26])=[O:24].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[Cl:1][C:2]1[CH:13]=[C:12]([F:14])[C:11]([NH:15][C:16]([NH:18][CH:21]=[C:22]([C:23]([O:25][CH3:26])=[O:24])[CH3:27])=[O:17])=[CH:10][C:3]=1[C:4]([O:6][CH:7]([CH3:9])[CH3:8])=[O:5]

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 3019052Methyl 3-methoxy-2-methyl-acrylateHCID 20130672Isopropyl 2-chloro-4-fluoro-5-ureidobenzoate

Product 1

HCID 54564066Isopropyl 2-chloro-4-fluoro-5-{3-[2-(methoxycarbonyl)propenyl]ureido}-benzoate

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

27.4 g of isopropyl 2-chloro-4-fluoro-5-ureidobenzoate and 13.0 g of methyl 3-methoxy-2-methyl-acrylate are heated under reflux for 2 hours in 250 ml of benzene with 1.9 g of toluene-4-sulphonic acid monohydrate. The reaction mixture is evaporated to dryness under reduced pressure and the residue is stirred with 400 ml of diethyl ether. The insoluble material is filtered off under suction and the filtrate is evaporated to dryness under reduced pressure. The residue is purified by chromatography on 1 kg of silica gel using ethyl acetate/n-hexane (1:3) as the eluent. There is obtained isopropyl 2-chloro-4-fluoro-5-{3-[2-(methoxycarbonyl)propenyl]ureido}-benzoate, m.p. 189°-190° C.

Workup

  1. customThe reaction mixture is evaporated to dryness under reduced pressure
  2. filtrationThe insoluble material is filtered off under suction
  3. customthe filtrate is evaporated to dryness under reduced pressure
  4. customThe residue is purified by chromatography on 1 kg of silica gel

Sources & evidence

ORD record
ord-1b7786e7d43c4426bc5186fa683b7598
Source dataset
uspto-grants-1988_07
Patent number
US04760163

Reaction notes

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