O-Xylene → Piroxicam

HRID 1979975Notes

Reaction equation

HRID 1979975 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])[NH:4][C:3]=1[C:14]([O:16]CCOC)=O.[NH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1.[C:28]1(C)C(C)=CC=CC=1>>[CH3:28][N:4]1[S:5](=[O:12])(=[O:13])[C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[C:2]([OH:1])=[C:3]1[C:14]([NH:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1)=[O:16]

Participants

4

Reactant 3

HCID 7237O-XyleneHCID 104392-AminopyridineHCID 704814632-Methoxyethyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide

Product 1

HCID 54676228PiroxicamYield 96%

Procedure

2-Methoxyethyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (28 g., 0.089 mole) and 2-aminopyridine (9.26 g., 0.098 mole) were combined with 500 ml. of xylene in a 1 liter flask equipped with an addition funnel and a reflux, variable take-off distillation head. The stirred reaction mixture was heated to reflux and the xylene distilled at the rate of approximately 100 ml./hour, while maintaining the pot volume almost constant by the addition of fresh xylene. After 6 hours, the head temperature, which had been relatively constant at 134° C., rose to 142° C. and reflux rate slowed. The reaction mixture was then cooled in an ice-bath and the precipitated solids recovered by filtration, with hexane for transfer and wash, and dried at 45° C. in vacuo to yield piroxicam (28.5 g., 96%; m.p. 167°-174° C.).

Workup

  1. distillationa reflux, variable take-off distillation head
  2. customThe stirred reaction mixture
  3. temperaturewas heated
  4. temperatureto reflux
  5. distillationthe xylene distilled at the rate of approximately 100 ml
  6. temperature/hour, while maintaining the pot volume
  7. additionalmost constant by the addition of fresh xylene
  8. customhad been relatively constant at 134° C.
  9. customrose to 142° C.
  10. temperaturereflux rate
  11. temperatureThe reaction mixture was then cooled in an ice-bath
  12. filtrationthe precipitated solids recovered by filtration, with hexane for transfer
  13. washwash
  14. customdried at 45° C. in vacuo

Sources & evidence

ORD record
ord-ddb59c0dc3ff4cbf8f2485c1392b20d8
Source dataset
uspto-grants-1984_11
Patent number
US04483982

Reaction notes

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