Reaction #76429

Reaction equation

oxalyl chloride

[2-(2,2-Dimethylpropyl)benzoxazol-5-yl]acetic acid

[(2,2-dimethylpropyl)benzoxazol-5yl]acetic acid

5-amino-4-chloro-3-methylisothiazole

→

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

Yield 28.7%

Solvents

dichloromethane

ethyl acetate

Conditions

Workup

1. 1
   Otherthe solvent was removed in vacuo
2. 2
   Temperaturethe mixture was heated
3. 3
   Temperatureunder reflux for 2 hours
4. 4
   Washwashed with brine
5. 5
   DryingThe organic solution was dried over anhydrous magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   Otherthe filtrate was evaporated in vacuo
8. 8
   OtherThe residue was further purified by flash column chromatography on silica gel
9. 9
   Washeluting with a 2:1 mixture of hexane

Procedure

[2-(2,2-Dimethylpropyl)benzoxazol-5-yl]acetic acid [from step 7] (0.800 g, 0.003 mole) was suspended in dichloromethane (10 ml) and N,N-dimethylformamide (one drop) and oxalyl chloride (0.451 g, 0.004 mole) were added sequentially. The mixture was stirred for 2 hour and then the solvent was removed in vacuo. The residue was taken up in xylene (10 ml), 5-amino-4-chloro-3-methylisothiazole [from step 1] (0.829 g, 0.006 mole) was added and then the mixture was heated under reflux for 2 hours. The mixture was cooled to room temperature, diluted with ethyl acetate and washed with brine. The organic solution was dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was further purified by flash column chromatography on silica gel, eluting with a 2:1 mixture of hexane:ethyl acetate, to give N-(4-chloro-3-methylisothiazol-5-yl)-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]acetamide (0.325 g) as a pale orange solid, m.p. 144-145° C.

Source