Hydrogen Bromide → 4-Bromo-thiazole-5-carboxylic acid ethyl ester
Reaction equation
N[C:2]1[N:3]=[C:4](SC)[S:5][C:6]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8].N([O-])=O.[Na+].[BrH:18]>Cl.[Zn].[Cu]Br>[Br:18][C:2]1[N:3]=[CH:4][S:5][C:6]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Procedure
Ethyl 2-mercaptoacetate is reacted with dimethyl N-cyanodithioimino-carbonate under the action of N-ethyldiisopropylamine in dimethylformamide to give ethyl 4-amino-2-methylthiothiazole-5-carboxylate, according to the method of Gompper, et al., Tet. Letters, 1885 (1966). Selective desulfurization is accomplished by the procedure of Baldwin and Ponticello, J. Med. Chem., 23(1), 65 (1980) by stirring at ambient temperature with zinc dust in 3N hydrochloric acid. The resultant ethyl 4-aminothiazole-5-carboxylate is nitrosated by the slow addition of sodium nitrite to a solution in 48% hydrobromic acid containing copper (I) bromide to give ethyl 4-bromothiazole-5-carboxylate. Heating an ethanolic solution of the bromide with the compound resulting from Example 21A and N-ethyldiisopropylamine in a sealed tube by the procedure described in Example 11B gives the fully protected product. This compound is deprotected by the procedure described in Example 11C and hydrolyzed by the procedure described in Example 12 to give the title compound.
Sources & evidence
- ORD record
- ord-809d3253e959479198bd6b340e3d45b0
- Source dataset
- uspto-grants-1994_07
- Patent number
- US05326776
Reaction notes
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