3-Chloroaniline → N-(3-chlorophenyl)-2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methylpropanamide

HRID 377572Notes

Reaction equation

HRID 377572 reaction equation
[CH3:1][C:2]1[O:7][CH2:6][N:5]([C:8]([CH3:13])([CH3:12])[C:9]([OH:11])=O)[C:4](=[O:14])[C:3]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:40][C:41]1[CH:42]=[C:43]([CH:45]=[CH:46][CH:47]=1)[NH2:44].C(N(CC)CC)C>ClC(Cl)(Cl)Cl.ClCCl>[Cl:40][C:41]1[CH:42]=[C:43]([NH:44][C:9](=[O:11])[C:8]([N:5]2[C:4](=[O:14])[C:3]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[C:2]([CH3:1])[O:7][CH2:6]2)([CH3:13])[CH3:12])[CH:45]=[CH:46][CH:47]=1

Participants

7

Reactant 4

HCID 79323-ChloroanilineHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 221182822-methyl-2-(6-methyl-5-phenyl-2,3-dihydro-4-oxo-4H-1,3-oxazin-3-yl)-propionic acid

Product 1

HCID 19354647N-(3-chlorophenyl)-2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methylpropanamideYield 74.9%

Reagents, catalysts & solvents 2

HCID 5943Carbon TetrachlorideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methylpropanoic acid (27.5 g) and triphenylphosphine (34.5 g) in tetrachloromethane (173 ml) and dichloromethane was heated at reflux for 45 minutes. The reaction mixture was cooled in an ice bath and 3-chloroaniline (12.8 g) and then triethylamine (14.0 ml) were added dropwise with stirring. The mixture was stirred at ambient temperature for 2 hours and evaporated under reduced pressure. The residue was suspended in ethyl acetate and the insoluble material removed by filtration. The filtrate was evaporated under reduced pressure and the residue purified by chromatography on silica gel, eluting with ethyl acetate/hexane to give N-(3-chlorophenyl)-2-(2,3-dihydro-6-methyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methylpropanamide (28.8 g) as a white solid, m.p. 146.5-149.9° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 45 minutes
  3. temperatureThe reaction mixture was cooled in an ice bath
  4. stirringThe mixture was stirred at ambient temperature for 2 hours
  5. customevaporated under reduced pressure
  6. customthe insoluble material removed by filtration
  7. customThe filtrate was evaporated under reduced pressure
  8. customthe residue purified by chromatography on silica gel
  9. washeluting with ethyl acetate/hexane

Sources & evidence

ORD record
ord-4e871f200c184f72a4d7072531023193
Source dataset
uspto-grants-2000_02
Patent number
US06028032

Reaction notes

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