Methane → Methyl 5-chloro-3-(methylsulfamoyl)thiophene-2-carboxylate

HRID 1448585Notes

Reaction equation

HRID 1448585 reaction equation
Cl[C:2]1SC2C(O)=C(C(OC)=O)N(C)S(=O)(=O)C=2C=1.NC1C=CC=CN=1.[Cl:26][C:27]1[S:31][C:30]([C:32]([OH:34])=[O:33])=[C:29]([S:35](=[O:39])(=[O:38])[NH:36][CH3:37])[CH:28]=1.C.ClC1SC2C(O)=C(C(=O)NC3C=CC=CN=3)N(C)S(=O)(=O)C=2C=1>OCC(CO)O.C1(C)C(C)=CC=CC=1>[Cl:26][C:27]1[S:31][C:30]([C:32]([O:34][CH3:2])=[O:33])=[C:29]([S:35](=[O:38])(=[O:39])[NH:36][CH3:37])[CH:28]=1

Participants

8

Reactant 5

HCID 297MethaneHCID 104392-AminopyridineHCID 203802625-Chloro-3-(methylsulfamoyl)thiophene-2-carboxylic acidHCID 546900316-Chloro-4-hydroxy-2-methyl-N-(pyridin-2-yl)-2H-thieno[3,2-e]-1,2-thiazine-3-carboxamide 1,1-dioxideHCID 54697517Methyl 6-chloro-4-hydroxy-2-methyl-1,1-dioxo-1,2-dihydro-1lambda~6~-thieno[2,3-e][1,2]thiazine-3-carboxylate

Product 1

HCID 17609505Methyl 5-chloro-3-(methylsulfamoyl)thiophene-2-carboxylate

Reagents, catalysts & solvents 2

HCID 753GlycerolSolventHCID 7237O-XyleneSolvent

Procedure

1200 ml. of absolute xylene are placed in a 2 liter volume flask and 11 g. of 6-chloro-4-hydroxy-2-methyl-3-methoxycarbonyl-2H-thieno[2,3-e]-1,2-thiazine-1,1-dioxide are added while stirring. 4.42 g. of 2-aminopyridine are next added and the solution is then boiled under reflux until all the starting product has been shown by thin layer chromatography to have reacted (about 4 hours). A gentle stream of nitrogen is passed through the mixture during boiling under reflux, in order to entrain the methanol that is formed. After the end of the reaction, the solution is cooled to about 120°, activated charcoal is added, and the solution is boiled for an additional short time. A hot water funnel is filled with glycerol and preheated to 120°, and the hot reaction solution at 120° is then filtered through this funnel. When the temperature of the solution has fallen to 70°, the solution is then scratched, whereupon small orange crystals begin to separate out. When cold, the solution is kept for 12 hours in an icebox (-5°) and the precipitate that has separated out is filtered under suction and washed with xylene. The product is dried in vacuo (1 mm, 120°, 2 hours). The orange to yellow crystals thus obtained are 6-chloro-4-hydroxy-2-methyl-3-(2-pyridylcarbamoyl)-2H-thieno[2,3-e]-1,2-thiazine-1,1-dioxide with a melting point of 225°-230° (with decomposition).

Workup

  1. temperatureunder reflux until all the starting product
  2. customto have reacted (about 4 hours)
  3. temperatureunder reflux, in order
  4. customis formed
  5. customAfter the end of the reaction
  6. temperaturethe solution is cooled to about 120°
  7. custompreheated to 120°
  8. filtrationthe hot reaction solution at 120° is then filtered through this funnel
  9. customhas fallen to 70°
  10. customto separate out
  11. customthe precipitate that has separated out
  12. filtrationis filtered under suction
  13. washwashed with xylene
  14. customThe product is dried in vacuo (1 mm, 120°, 2 hours)
  15. customThe orange to yellow crystals thus obtained

Sources & evidence

ORD record
ord-19868e786c9e44dfbd4e2da7868a140f
Source dataset
uspto-grants-1979_12
Patent number
US04180662

Reaction notes

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