Water → HCID 11812072, compound

HRID 377552Notes

Reaction equation

HRID 377552 reaction equation
[CH3:1][S:2][CH2:3][C:4]1[O:9][CH2:8][N:7]([C:10]([CH3:15])([CH3:14])[C:11](O)=[O:12])[C:6](=[O:16])[C:5]=1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[F:23][C:24]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:25]=1[NH2:26].O>CN(C)C=O.C(OCC)(=O)C>[F:23][C:24]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:25]=1[NH:26][C:11](=[O:12])[C:10]([N:7]1[C:6](=[O:16])[C:5]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:4]([CH2:3][S:2][CH3:1])[O:9][CH2:8]1)([CH3:14])[CH3:15]

Participants

6

Reactant 3

HCID 962WaterHCID 677752,5-DifluoroanilineHCID 11141777HCID 11141777, compound

Product 1

HCID 11812072HCID 11812072, compoundYield 7.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of dicyclohexylcarbodiinide (10.04 g) in N,N-dimethyeformaeide was added to a stirred solution of 2-(2,3-dihydro-6-methylthiomethyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methylpropanoic acid (13.00 g) in N,N-dimethylformamide at 20° C. 2,5-Difluoroaniline (7.84 g) was added to the solution at 20° C. and the solution was stirred at ambient temperature for 18 hours. The reaction mixture was diluted with ethyl acetate then added to water and the fine suspension removed by filtration. The organic layer was washed in turn with 0.5M hydrochloric acid, brine, 1.0M sodium carbonate and brine and then dried (magnesium sulphate). The organic solution was evaporated under reduced pressure and the residue was purified by chromatography on silica gel, eluting with dichioromethane to give N-(2,5-difluorophenyl)-2-(2,3-dihydro-6-methylthiomethyl-4-oxo-5-phenyl-4H-1,3-oxazin-3-yl)-2-methylpropanamide (Compound 3, 1.35 g) as a yellow solid, NMR (CDCl3) 1.68(s,6H), 2.10(s,3H), 3.22(s,2H), 5.30(s,2H), 6.64-6.76(m,1H), 6.95-7.05(m,1H), 7.25-7.38(m,5H), 8.11-8.21(m,2H).

Workup

  1. customthe fine suspension removed by filtration
  2. washThe organic layer was washed in turn with 0.5M hydrochloric acid, brine, 1.0M sodium carbonate and brine
  3. dry with materialdried (magnesium sulphate)
  4. customThe organic solution was evaporated under reduced pressure
  5. customthe residue was purified by chromatography on silica gel
  6. washeluting with dichioromethane

Sources & evidence

ORD record
ord-bd89b1a2a19545349439ed72b4fdfe9e
Source dataset
uspto-grants-2000_02
Patent number
US06028032

Reaction notes

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