Reaction #76453

Reaction equation

ammonium chloride

5-Amino-4-chloro-3-methylisothiazole

sodium methoxide

methyl 2-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]-2-fluoropropionate

→

desired product

Yield 82.0%

N-(4-chloro-3-methylisothiazol-5-yl)-2-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]-2-fluoropropionamide

Yield 82.0%

Solvents

tetrahydrofuran

water

tetrahydrofuran

Conditions

Workup

1. 1
   workup.STIRRINGdropwise, and the mixture was stirred at room temperature for 3 hours
2. 2
   Extractionextracted with ethyl acetate
3. 3
   ExtractionThe organic extract
4. 4
   Dryingwas dried over anhydrous magnesium sulfate
5. 5
   Filtrationfiltered
6. 6
   Otherthe filtrate was evaporated in vacuo
7. 7
   OtherThe residue was purified by flash column chromatography on silica gel
8. 8
   Washeluting with ethyl acetate:hexane 12:88

Procedure

5-Amino-4-chloro-3-methylisothiazole (0.28 g, 0.00188 mol) was added to a suspension of sodium methoxide (0.24 g, 0.004 mol) in tetrahydrofuran (6 ml) and the mixture was stirred at room temperature for 20 minutes. A solution of methyl 2-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]-2-fluoropropionate (0.50 g, 0.00171 mol) in tetrahydrofuran (2 ml) was added, dropwise, and the mixture was stirred at room temperature for 3 hours. The mixture was diluted with water, acidified with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic extract was 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:hexane 12:88, to give the desired product (0.575 g) as a pale yellow gum.

Source