3-Amino-5-methylisoxazole → Isoxicam

HRID 2398040Notes

Reaction equation

HRID 2398040 reaction equation
[OH:1][C:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[S:5](=[O:13])(=[O:12])[N:4]([CH3:14])[C:3]=1[C:15]([O:17]C)=O.[NH2:19][C:20]1[CH:24]=[C:23]([CH3:25])[O:22][N:21]=1>C1(C)C(C)=CC=CC=1>[OH:1][C:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[S:5](=[O:12])(=[O:13])[N:4]([CH3:14])[C:3]=1[C:15](=[O:17])[NH:19][C:20]1[CH:24]=[C:23]([CH3:25])[O:22][N:21]=1

Participants

4

Reactant 2

HCID 661723-Amino-5-methylisoxazoleHCID 54676532methyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide

Product 1

HCID 54677972Isoxicam

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Conditions

Temperature
25 °C

Procedure

To an appropriate flask equipped for reflux and/or distillation, 900 ml xylene, 40 grams (.149 moles) methyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide and 19.94 grams (.203 moles) of 3-amino-5-methylisoxazole are added. The mixture is refluxed for 13-18 hours. At one hour intervals, about 3-4% of the solvent volume is distilled off. Every 4 to 5 hours fresh xylene is added, equal in amount to that distilled during this period. At the end of the heating period, the reaction is cooled to 25° C., filtered and the cake is washed with xylene. After drying, the crude product weighed 43.8 grams (88%). This material could be recrystallized from about 40-50 volumes of dioxane with an 80-85% recovery of acceptable material. An alternate procedure for the purification of crude product is as follows:

Workup

  1. customTo an appropriate flask equipped
  2. temperaturefor reflux
  3. additionare added
  4. temperatureThe mixture is refluxed for 13-18 hours
  5. distillationAt one hour intervals, about 3-4% of the solvent volume is distilled off
  6. additionEvery 4 to 5 hours fresh xylene is added, equal in amount to
  7. distillationthat distilled during this period
  8. filtrationfiltered
  9. washthe cake is washed with xylene
  10. customAfter drying
  11. customThis material could be recrystallized from about 40-50 volumes of dioxane with an 80-85% recovery of acceptable material
  12. customAn alternate procedure for the purification of crude product

Sources & evidence

ORD record
ord-16091dbb98e346cdbb08b78590d4cbef
Source dataset
uspto-grants-1977_05
Patent number
US04024136

Reaction notes

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