تفاعل #74604

معادلة التفاعل

5-chloro-2,4-difluorobenzenesulfonyl chloride

N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine

lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide

→

title compound

5-Chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

المذيبات

tetrahydrofuran

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةbefore cooling to −70° C
2. 2
   workup.ADDITIONAfter complete addition
3. 3
   درجة الحرارةthe reaction mixture was gradually warmed to room temperature
4. 4
   workup.STIRRINGstirred for 1 hour
5. 5
   أخرىReaction mixture
6. 6
   أخرىwas quenched with saturated aqueous ammonium chloride solution
7. 7
   استخلاصextracted with ethyl acetate
8. 8
   غسيلOrganic layer was washed with water and saturated aqueous sodium chloride solution
9. 9
   أخرىCrude residue was purified by column chromatography
10. 10
    غسيلeluting with ethyl acetate

الإجراء التجريبي

To a solution of (N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (Preparation 14, 40.6 g, 0.1619 mol) in anhydrous tetrahydrofuran (600. mL), cooled to −70° C., under nitrogen was added lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (1 M in tetrahydrofuran, 161.9 mL, 0.161.9 mol) drop wise. The reaction mixture was warmed to room temperature and stirred for 1 hour before cooling to −70° C. A solution of 5-chloro-2,4-difluorobenzenesulfonyl chloride (40 g, 0.1619 mol) in tetrahydrofuran (200.0 mL) was added dropwise. After complete addition, the reaction mixture was gradually warmed to room temperature and stirred for 1 hour. Reaction mixture was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. Organic layer was washed with water and saturated aqueous sodium chloride solution. Crude residue was purified by column chromatography eluting with ethyl acetate:hexane (gradient 1:19 to 3:17, by volume) to afford the title compound as a white solid, 46 g.

المصدر