Anthranilic Acid → 2-(3-chlorophenylamino)-6-octyl-4H-3,1-benzoxazin-4-one

HRID 430949

Reaction equation

HRID 430949 reaction equation
[C:1]([OH:10])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[NH2:4].[Cl:11][C:12]1[CH:13]=[C:14]([N:18]=[C:19]=O)[CH:15]=[CH:16][CH:17]=1.O1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[CH2:24][C:23](=O)N1.NC(N)=O>C1COCC1>[Cl:11][C:12]1[CH:13]=[C:14]([NH:18][C:19]2[O:9][C:1](=[O:10])[C:2]3[CH:8]=[C:7]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH:6]=[CH:5][C:3]=3[N:4]=2)[CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 227Anthranilic AcidHCID 1176UreaHCID 17968Benzene, 1-chloro-3-isocyanato-HCID 199374482H-1,2-Benzoxazin-3(4H)-one

Product 1

HCID 187626302-(3-chlorophenylamino)-6-octyl-4H-3,1-benzoxazin-4-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The anthranilic acid (200 mg, 0.8 mmol) was dissolved in anhydrous THF (1 ml), and to this was added 3-chlorophenylisocyanate (117 μl, 0.96 mmol). The mixture was stirred for 3 h before being concentrated. The residue was partitioned between water and ethyl acetate. The organic layer was washed with 5% aqueous citric acid, saturated aqueous sodium bicarbonate and brine then dried (MgSO4) and concentrated to give an orange solid. This was purified by flash chromatography on silica (15% EtOAc/hexane to 100% EtOAc, then 10% EtOH/EtOAc) which gave, in order of elution, the benzoxazinone (18 mg, 0.05 mmol); δH (400 MHz, CDCl3) 0.77-0.82 (3H, m, Me), 1.19-1.24 (10H, m, 5×CH2), 1.55-1.57 (2H, m, ArCH2CH2), 2.56-2.62 (2H, m, ArCH2), 7.00-7.32 (4H, m, 3×ArH, NH), 7.40-7.49 (2H, m, 2×ArH), 7.81-7.83 (2H, m, ArH); m/z (ES+) 385 (MH+) and the urea (160 mg, 0.4 mmol); m/z (ES−) 401 (M−H)−.

Workup

  1. concentrationbefore being concentrated
  2. customThe residue was partitioned between water and ethyl acetate
  3. washThe organic layer was washed with 5% aqueous citric acid, saturated aqueous sodium bicarbonate and brine
  4. dry with materialthen dried (MgSO4)
  5. concentrationconcentrated
  6. customto give an orange solid
  7. customThis was purified by flash chromatography on silica (15% EtOAc/hexane to 100% EtOAc
  8. custom10% EtOH/EtOAc) which gave, in order of elution

Sources & evidence

ORD record
ord-4003d3bed4964987a4570d398919c426
Source dataset
uspto-grants-2003_12
Patent number
US06656934B2

Linked notes

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