Sodium Methoxide → N-(4-chloro-3-methylisothiazol-5-yl)-2-(4-methoxyphenyl)propionamide

HRID 48158Notes

Reaction equation

HRID 48158 reaction equation
[NH2:1][C:2]1[S:6][N:5]=[C:4]([CH3:7])[C:3]=1[Cl:8].C[O-].[Na+].[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]([CH3:25])[C:21](OC)=[O:22])=[CH:16][CH:15]=1>O1CCCC1>[Cl:8][C:3]1[C:4]([CH3:7])=[N:5][S:6][C:2]=1[NH:1][C:21](=[O:22])[CH:20]([C:17]1[CH:18]=[CH:19][C:14]([O:13][CH3:12])=[CH:15][CH:16]=1)[CH3:25]

Participants

5

Reactant 3

HCID 10942334Sodium MethoxideHCID 112405714-Chloro-3-methyl-1,2-thiazol-5-amineHCID 12398855Methyl 2-(4-methoxyphenyl)propanoate

Product 1

HCID 22742110N-(4-chloro-3-methylisothiazol-5-yl)-2-(4-methoxyphenyl)propionamideYield 89.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

5-Amino-4-chloro-3-methylisothiazole (7.4 g, 0.050 mol) was added to a suspension of sodium methoxide (6.1 g, 0.112 mol) in tetrahydrofuran (160 ml) and the mixture was stirred at room temperature for 20 minutes. A solution of methyl 2-(4-methoxyphenyl)propionate (8.8 g, 0.045 mol) in tetrahydrofuran (40 ml) was added dropwise and the mixture was stirred for 3 hours at room temperature. The reaction was quenched with water, acidified with dilute aqueous hydrochloric acid and extracted with ethyl acetate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate:dichloromethane 2.5:97.5, to give N-(4-chloro-3-methylisothiazol-5-yl)-2-(4-methoxyphenyl)propionamide (12.5 g) as a colourless solid.

Workup

  1. stirringthe mixture was stirred for 3 hours at room temperature
  2. customThe reaction was quenched with water
  3. extractionextracted with ethyl acetate
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customthe filtrate was evaporated in vacuo
  9. customThe residue was purified by flash column chromatography on silica gel
  10. washeluting with ethyl acetate:dichloromethane 2.5:97.5

Sources & evidence

ORD record
ord-94f758ee0994470e84b39c2dac1f30ae
Source dataset
uspto-grants-2004_03
Patent number
US06703347B2

Reaction notes

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