Water → Methyl 4-(4-chloro-2-(1-cyclopropylethylcarbamoyl)phenylamino)-4-oxocrotonate

HRID 448821Notes

Reaction equation

HRID 448821 reaction equation
Cl.[CH:2]1([CH:5]([NH2:7])[CH3:6])[CH2:4][CH2:3]1.C(N(CC)CC)C.[Cl:15][C:16]1[CH:32]=[CH:31][C:19]2[N:20]=[C:21](/[CH:25]=[CH:26]/[C:27]([O:29][CH3:30])=[O:28])[O:22][C:23](=[O:24])[C:18]=2[CH:17]=1.O>C(#N)C.C(OCC)(=O)C>[Cl:15][C:16]1[CH:32]=[CH:31][C:19]([NH:20][C:21](=[O:22])/[CH:25]=[CH:26]/[C:27]([O:29][CH3:30])=[O:28])=[C:18]([C:23](=[O:24])[NH:7][CH:5]([CH:2]2[CH2:4][CH2:3]2)[CH3:6])[CH:17]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 13927266methyl (E)-3-(6-chloro-4-oxo-4H-benzo[d][1,3]oxazin-2-yl)acrylateHCID 162478691-Cyclopropylethylamine hydrochloride

Product 1

HCID 44185603Methyl 4-(4-chloro-2-(1-cyclopropylethylcarbamoyl)phenylamino)-4-oxocrotonate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixed solution of 0.73 g of 1-cyclopropylethylamine hydrochloride and 0.91 g of triethylamine in 12 ml of acetonitrile was stirred at room temperature for one hour. Then, to the mixed solution, 0.53 g of crude crystals of methyl (E)-3-(6-chloro-4-oxo-4H-benzo[d][1,3]oxazin-2-yl)acrylate were added at room temperature and reacted for 3 hours at room temperature. To the reaction liquid, water was added, and then ethyl acetate was added for extraction. The organic layer was washed with a saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressed, and the residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=9/1 to 8/2) to obtain 0.22 g of the desired product having a slightly yellow color (melting point: 154.4° C.).

Workup

  1. customreacted for 3 hours at room temperature
  2. additionwas added
  3. washThe organic layer was washed with a saturated sodium chloride aqueous solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off
  6. customthe residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=9/1 to 8/2)

Sources & evidence

ORD record
ord-b0436f365e064f189be42a580ea0c529
Source dataset
uspto-grants-2013_07
Patent number
US08481744B2

Reaction notes

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