Sulfuric Acid → Ethyl 5-sulfanyl-1,3,4-thiadiazole-2-carboxylate
Reaction equation
[CH2:1]([O:3][C:4](=[O:9])[C:5]([NH:7][NH2:8])=O)[CH3:2].[C:10](=[S:12])=[S:11].[OH-].[K+].S(=O)(=O)(O)O>C(O)C>[CH2:1]([O:3][C:4]([C:5]1[S:11][C:10]([SH:12])=[N:8][N:7]=1)=[O:9])[CH3:2]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 55 °C
Procedure
Scheme 1 shows a synthetic method that may be used to prepare compounds of formula I-III. First, hydrazino-oxo-acetic acid ethyl ester 1 (prepared by the method of Berdinskii, I. S.; Maslivets, A. N. Hydrazides of disubstituted glycolic acids. Zh. Org. Khim. (1982), 18(9), 1839-43) is treated with carbon disulfide (excess) and KOH (1.0 equiv.) in ethanol at 0° C. to give 2. Treatment of 2 with cold (excess) sulfuric acid for 20 minutes followed by heating to 55° C. for 1 hour gives 5-mercapto-[1,3,4]-thiadiazole-2-carboxylic acid ethyl ester which is then treated with ethyl iodide and potassium carbonate in ethanol/water at room temperature to give 3. Heating compound 4 in the presence of benzylamine gives the amide, which is oxidized to the sulfone 5 with m-chloroperbenzoic acid (2.5 equiv) in chloroform or methylene chloride at room temperature. Treatment of 5 with 3-oxo-pentanoic acid methyl ester and excess sodium hydride in refluxing tert-butanol for 48 hours gives 6 after flash silica purification.
Workup
- customto prepare compounds of formula I-III
- customto give 2
Sources & evidence
- ORD record
- ord-50eebc110b424265b488c8f1961f094f
- Source dataset
- uspto-grants-2005_05
- Patent number
- US06897223B2
Reaction notes
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