Phosphorus oxychloride → 4-(4-Chloro-6-methoxy-3-nitroquinolin-7-yl)-3,5-dimethylisoxazole

HRID 81979Notes

Reaction equation

HRID 81979 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:16]=[C:15]3[C:10]([C:11](=O)[C:12]([N+:17]([O-:19])=[O:18])=[CH:13][NH:14]3)=[CH:9][C:8]=2[O:21][CH3:22])=[C:5]([CH3:23])[O:4][N:3]=1.O=P(Cl)(Cl)[Cl:26]>>[Cl:26][C:11]1[C:10]2[C:15](=[CH:16][C:7]([C:6]3[C:2]([CH3:1])=[N:3][O:4][C:5]=3[CH3:23])=[C:8]([O:21][CH3:22])[CH:9]=2)[N:14]=[CH:13][C:12]=1[N+:17]([O-:19])=[O:18]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 574655797-(3,5-Dimethyl-4-isoxazolyl)-6-(methoxy)-3-nitro-4-quinolinol

Product 1

HCID 574655804-(4-Chloro-6-methoxy-3-nitroquinolin-7-yl)-3,5-dimethylisoxazoleYield 63.4%

Conditions

Temperature
110 °C

Procedure

7-(3,5-Dimethylisoxazol-4-yl)-6-methoxy-3-nitroquinolin-4(1H)-one (for a preparation see Intermediate 6) (4.78 g, 15.16 mmol) was dissolved in POCl3 (10 ml, 107 mmol) and the mixture was heated at 110° C. for 3 h, then cooled and evaporated in vacuo, The residue was suspended in toluene (20 ml) and evaporated in vacuo, then the residue was suspended in DCM (100 ml) and saturated sodium hydrogen carbonate solution (100 ml) and stirred for 10 min. The organic layer was dried and evaporated and the residue dissolved in DCM (10 ml) and loaded onto a 100 g silica column, then eluted with 0-60% EtOAc/cyclohexane to give 4-(4-chloro-6-methoxy-3-nitroquinolin-7-yl)-3,5-dimethylisoxazole (3.21 g, 9.62 mmol, 63.4% yield) as a bright yellow powder. LCMS (formate) Rt 1.13 min, MH+ 334

Workup

  1. temperaturecooled
  2. customevaporated in vacuo
  3. customevaporated in vacuo
  4. customThe organic layer was dried
  5. customevaporated
  6. dissolutionthe residue dissolved in DCM (10 ml)
  7. washeluted with 0-60% EtOAc/cyclohexane

Sources & evidence

ORD record
ord-169079e450f045bab521670a164e37ef
Source dataset
uspto-grants-2014_09
Patent number
US08846709B2

Reaction notes

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