Ethyl Thioglycolate → Methyl 7-bromo-3,4-dihydro-3-oxo-2H-pyrido[3,2-b]-1,4-thiazine-6-carboxylate

HRID 639025Notes

Reaction equation

HRID 639025 reaction equation
[SH:1][CH2:2][C:3](OCC)=[O:4].[H-].[Na+].[NH2:10][C:11]1[N:16]=[C:15]([C:17]([O:19][CH3:20])=[O:18])[C:14]([Br:21])=[CH:13][C:12]=1Br>CN(C=O)C>[Br:21][C:14]1[C:15]([C:17]([O:19][CH3:20])=[O:18])=[N:16][C:11]2[NH:10][C:3](=[O:4])[CH2:2][S:1][C:12]=2[CH:13]=1

Participants

5

Reactant 3

HCID 12185Ethyl ThioglycolateHCID 24758Sodium hydrideHCID 10495131Methyl 6-amino-3,5-dibromopicolinate

Product 1

HCID 21873784Methyl 7-bromo-3,4-dihydro-3-oxo-2H-pyrido[3,2-b]-1,4-thiazine-6-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of ethyl 2-mercaptoacetate (18.4 ml) in DMF (650 ml) was ice-cooled and treated with sodium hydride (6.78 g of a 60% dispersion in oil). After 1 hour methyl 6-amino-3,5-dibromopyridine-2-carboxylate (50 g) (T. R. Kelly and F. Lang, J. Org. Chem. 61, 1996, 4623-4633) was added and the mixture stirred for 16 hours at room temperature. The solution was partitioned between EtOAc and water (2 liters each), shaken, separated and the EtOAc along with solid that crystallised out washed with water (2×1 liter). The EtOAc was evaporated to low volume, solid filtered, washed with water and EtOAc and dried. The filtrate was separated, EtOAc dried and evaporated. The residue was taken up in AcOH and heated to 100° C. overnight, then evaporated. The white solid was triturated uder EtOAc, filtered off, washed with a little EtOAc and dried (Na2SO4). Combining the 2 batches of ester gave 33.35 g (70%). MS (APCl−) m/z 223 ([M−H]−, 100%).

Workup

  1. temperaturecooled
  2. addition61, 1996, 4623-4633) was added
  3. customThe solution was partitioned between EtOAc and water (2 liters each)
  4. stirringshaken
  5. customseparated
  6. customthe EtOAc along with solid that crystallised
  7. washout washed with water (2×1 liter)
  8. customThe EtOAc was evaporated to low volume, solid
  9. filtrationfiltered
  10. washwashed with water and EtOAc
  11. customdried
  12. customThe filtrate was separated
  13. dry with materialEtOAc dried
  14. customevaporated
  15. temperatureheated to 100° C. overnight
  16. customevaporated
  17. customThe white solid was triturated uder EtOAc
  18. filtrationfiltered off
  19. washwashed with a little EtOAc
  20. dry with materialdried (Na2SO4)
  21. customgave 33.35 g (70%)

Sources & evidence

ORD record
ord-3b64af322909436b9c520cb4581a45c1
Source dataset
uspto-grants-2010_04
Patent number
US07691850B2

Reaction notes

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