Ethyl thiooxamate → HCID 22605375, compound

HRID 1281738Notes

Reaction equation

HRID 1281738 reaction equation
BrC[CH2:3][C:4]([C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1)=O.[CH2:16]([O:18][C:19](=[O:23])[C:20]([NH2:22])=[S:21])[CH3:17]>CCO>[CH:7]1[C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:14]=[CH:15][C:6]=1[C:4]1[N:22]=[C:20]([C:19]([O:18][CH2:16][CH3:17])=[O:23])[S:21][CH:3]=1

Participants

4

Reactant 2

HCID 2733398Ethyl thiooxamateHCID 82136344HCID 82136344, compound

Product 1

HCID 22605375HCID 22605375, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of bromoethyl-2-naphthyl ketone (1.78 g, 6.8 mmol), 2-thio-oxalamic acid ethyl ester (1 g, 7.5 mmol) in EtOH (absolute) was kept under reflux for 6 h. The mixture was cooled to room temperature. The product separated as a solid, which was filtered, washed with ethanol and dried to provide the desired ester, ethyl 4-(2-naphthyl)-1,3-thiazole-2-carboxylate, (IIIb) (0.862 g, 48% yield). MS: 284 (M+H). To a mixture of the ester, (IIIb) (800 mg, 2.82 mmol) in dry methylacetate (10 mL) was added NaH (60% dispersion in mineral oil, 135 mg, 3.37 mmol). The mixture was stirred at room temperature for 0.5 h and at reflux for 2 h. The mixture was poured into cold water and was neutralized with conc. HCl. After saturating the mixture with NaCl, the mixture was extracted from dichloromethane (twice). The combined extract was washed with brine. After drying over magnesium sulphate, solvent was evaporated to furnish the β-ketoester, ethyl 3-(4-(2-naphthyl)(1,3-thiazol-2-yl))-3-oxopropanoate, which was used for the next step without further purification. To the above β-ketoester was added absolute ethanol (10 mL) and hydrazine hydrate (1 mL, excess). The mixture was kept under reflux for 4 h. After cooling, solvent was evaporated from the reaction mixture. The resulting mixture was chromatographed over silica gel and was eluted with EtOAc. The product pyrazolone (VIg) was isolated as a solid which was further purified via washing with diethyl ether (i.e. stirring in ˜50 mL of diethyl ether followed by filtration and washing with diethyl ether). Yield 287 mg, (35% in two steps). MS: 294 (M+H).

Workup

  1. temperatureunder reflux for 6 h
  2. customThe product separated as a solid, which
  3. filtrationwas filtered
  4. washwashed with ethanol
  5. customdried

Sources & evidence

ORD record
ord-c0f8641604204175ac917ecdcfe2805b
Source dataset
uspto-grants-2002_09
Patent number
US06455525B1

Reaction notes

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