Diketene → HCID 86621302, compound

HRID 914399Notes

Reaction equation

HRID 914399 reaction equation
[C:1]([O:5][C:6](=[O:19])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][CH2:17][NH2:18])[N:15]=1)([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[CH2:20]=[C:21]1[O:25][C:23](=[O:24])[CH2:22]1>CN(C)C=O.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:19])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][CH2:17][NH:18][C:23](=[O:24])[CH2:22][C:21]([CH3:20])=[O:25])[N:15]=1)([CH3:9])[CH3:8])([CH3:2])([CH3:4])[CH3:3]

Participants

5

Reactant 2

HCID 12661DiketeneHCID 597594492-{[4-(2-Aminoethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid tert-butyl ester

Product 1

HCID 86621302HCID 86621302, compoundYield 88.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-{[4-(2-Aminoethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid tert-butyl ester (3.0 g) synthesized in Example 7 was dissolved in N,N-dimethylformamide (50 mL), and diketene (0.88 g) was added dropwise under ice-cooling. After raising to room temperature, the mixture was stirred for one hour. The mixture was diluted with ethyl acetate, and the organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give 2-({4-[2-(acetoacetylamino)ethyl]-1,3-thiazol-2-yl}thio)-2-methylpropionic acid tert-butyl ester (3.4 g) as a colorless oil. This compound was used in the next step without particular purification. [4-(Trifluoromethoxy)phenyl]hydrazine hydrochloride (390 mg) was dissolved in ethanol (8 mL), pulverized sodium hydroxide (65 mg) was added at room temperature. The insoluble material was filtered through celite, and the solvent was evaporated under reduced pressure. The residue was dissolved again in ethanol (8 mL), 2-({4-[2-(acetoacetylamino)ethyl]-1,3-thiazol-2-yl}thio)-2-methylpropionic acid tert-butyl ester (600 mg) obtained earlier was added at room temperature, and the mixture was stirred for 30 min. The solvent was evaporated under reduced pressure, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (8 mL), diphosphorus pentasulfide (345 mg) and sodium carbonate (329 mg) were added, and the mixture was heated under reflux for 2 hr. The solvent was evaporated, and the residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=4:1) to give the title compound (690 mg) as a colorless oil.

Workup

  1. temperaturecooling
  2. washthe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-10aa0094e24a43f0bd2dfe2cdb73a8f6
Source dataset
uspto-grants-2011_09
Patent number
US08026370B2

Reaction notes

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