Diketene → 2-[(4-{2-[Acetoacetyl(heptyl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester

HRID 914374Notes

Reaction equation

HRID 914374 reaction equation
[C:1]([O:5][C:6](=[O:26])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][CH2:17][NH:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[N:15]=1)([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[CH2:27]=[C:28]1[O:32][C:30](=[O:31])[CH2:29]1>CN(C)C=O.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:26])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][CH2:17][N:18]([C:30](=[O:31])[CH2:29][C:28]([CH3:27])=[O:32])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[N:15]=1)([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 12661DiketeneHCID 597593122-({4-[2-(Heptylamino)ethyl]-1,3-thiazol-2-yl}thio)-2-methylpropionic acid tert-butyl ester

Product 1

HCID 866213012-[(4-{2-[Acetoacetyl(heptyl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl esterYield 82.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-({4-[2-(Heptylamino)ethyl]-1,3-thiazol-2-yl}thio)-2-methylpropionic acid tert-butyl ester (3.41 g) synthesized in Example 303-2 was dissolved in N,N-dimethylformamide (43 mL), and diketene (0.75 g) was added dropwise under ice-cooling. After warming to room temperature, the mixture was stirred for one hour. The mixture was diluted with ethyl acetate. 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-[acetoacetyl(heptyl)amino]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester (3.4 g) as a colorless oil. The present compound was used in the next step without particular purification. The present compound (1.0 g) was dissolved in ethanol (10 mL), hydrazine monohydrate (0.103 g) was added thereto at room temperature, and the mixture was stirred overnight. The solvent was evaporated under reduced pressure, the residue was dissolved in tetrahydrofuran (10 mL), diphosphorus pentasulfide (0.459 g) and sodium carbonate (0.437 g) were added thereto, and the mixture was heated under reflux for 2 hr. The solvent was evaporated, and the residue was directly purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=1:1 to 1:2) to give the title compound (0.54 g) 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-7758e9848ce943da9519c832e5dfd703
Source dataset
uspto-grants-2011_09
Patent number
US08026370B2

Reaction notes

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