Triethylamine → 3-[2-(3,4-diethoxyphenyl)thiazole-4-yl]-N-methoxy-N-methylpropionamide

HRID 2097555Notes

Reaction equation

HRID 2097555 reaction equation
ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.Cl.[CH3:24][NH:25][O:26][CH3:27].C(N(CC)CC)C.[CH2:35]([O:37][C:38]1[CH:39]=[C:40]([C:47]2[S:48][CH:49]=[C:50]([CH2:52][CH2:53][C:54]([OH:56])=O)[N:51]=2)[CH:41]=[CH:42][C:43]=1[O:44][CH2:45][CH3:46])[CH3:36]>ClCCl.O>[CH2:35]([O:37][C:38]1[CH:39]=[C:40]([C:47]2[S:48][CH:49]=[C:50]([CH2:52][CH2:53][C:54]([N:25]([O:26][CH3:27])[CH3:24])=[O:56])[N:51]=2)[CH:41]=[CH:42][C:43]=1[O:44][CH2:45][CH3:46])[CH3:36]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68704548HCID 68704548, compound

Product 1

HCID 866183573-[2-(3,4-diethoxyphenyl)thiazole-4-yl]-N-methoxy-N-methylpropionamideYield 85.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

1-hydroxybenzotriazole (22.91 g, 149.6 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (WSC) (28.68 g, 149.6 mmol), N,O-dimethylhydroxylamine hydrochloride (13.93 g, 136 mmol) and triethylamine (41.7 ml, 299.2 mmol) were added to a solution (1.0 l) of 3-[2-(3,4-diethoxyphenyl)thiazole-4-yl]propionic acid (43.71 g, 136 mmol) in dichloromethane, followed by stirring at room temperature for 4 hours. Water was added to separate the reaction mixture into layers, and the aqueous layer was further subjected to extraction with dichloromethane. The organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/3). The solvent was distilled off under reduced pressure, and the residue was recrystallized from an ethyl acetate/n-hexane mixed solvent, to thereby obtain 42.4 g (yield: 68%) of 3-[2-(3,4-diethoxyphenyl)thiazole-4-yl]-N-methoxy-N-methylpropionamide as colorless prisms.

Workup

  1. customto separate the reaction mixture into layers
  2. extractionthe aqueous layer was further subjected to extraction with dichloromethane
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/3)
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe residue was recrystallized from an ethyl acetate/n-hexane mixed solvent

Sources & evidence

ORD record
ord-d3712368c1cb40abb168212de3406bdb
Source dataset
uspto-grants-2013_05
Patent number
US08450352B2

Reaction notes

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