Potassium Carbonate → 2-(7-Hydroxy-2-oxo-2H-chromen-3-yl)-4-methyl-thiazole-5-carboxylic acid ethyl ester

HRID 579441Notes

Reaction equation

HRID 579441 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:13](=[S:15])[NH2:14])[C:8](=[O:12])[O:9]2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH2:22]([O:24][C:25](=[O:31])[CH:26](Cl)[C:27](=O)[CH3:28])[CH3:23].C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>CN(C)C=O.O>[CH2:22]([O:24][C:25]([C:26]1[S:15][C:13]([C:7]2[C:8](=[O:12])[O:9][C:10]3[C:5]([CH:6]=2)=[CH:4][CH:3]=[C:2]([OH:1])[CH:11]=3)=[N:14][C:27]=1[CH3:28])=[O:31])[CH3:23]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 11858Ethyl 2-chloroacetoacetateHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 1355028867-hydroxy-2-oxo-2H-chromene-3-carbothioamide

Product 1

HCID 1363877712-(7-Hydroxy-2-oxo-2H-chromen-3-yl)-4-methyl-thiazole-5-carboxylic acid ethyl esterYield 14.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 7-hydroxy-2-oxo-2H-chromene-3-carbothioic acid amide (66 mg, 0.3 mmol) in anhydrous N,N-dimethylformamide (5 mL), freshly dried K2CO3 (263 mg, 1.9 mmol) was added followed by 2-chloro-3-oxo-butyric acid ethyl ester (79 μL, 94 mg, 0.54 mmol) and the mixture was stirred at room temperature for 19 h. The mixture was poured into water (25 mL) and extracted first with chloroform (3×10 mL) and, after saturation with NaCl, with tetrahydrofuran (3×10 mL). The combined organic extracts were dried over MgSO4 and concentrated. The residue was dissolved in chloroform (8 mL), pyridinium p-toluenesulfonate (7.5 mg, 0.03 mmol) was added and the mixture was stirred at 60° C. for 4.5 h. After cooling, the solution was washed with brine (3×5 mL), dried over MgSO4 and concentrated. The residue was purified by column chromatography on silica, eluting with a 9:1:0.1 mixture of chloroform, methanol and cc. NH4OH. The title compound (14.5 mg, 0.044 mmol, 14.7%) was obtained as a yellow solid.

Workup

  1. extractionextracted first with chloroform (3×10 mL)
  2. dry with materialThe combined organic extracts were dried over MgSO4
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in chloroform (8 mL)
  5. stirringthe mixture was stirred at 60° C. for 4.5 h
  6. temperatureAfter cooling
  7. washthe solution was washed with brine (3×5 mL)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography on silica
  11. washeluting with a 9:1:0.1 mixture of chloroform, methanol and cc

Sources & evidence

ORD record
ord-6f828a41fbab4672a925f846ee5ab1a5
Source dataset
uspto-grants-2015_05
Patent number
US09040714B2

Reaction notes

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