反应详情

温度

-78 °C

A 250-mL round bottom flask was charged with N-(4-methoxybenzyl)-1,2,4-thiadiazol-5-amine (INTERMEDIATE H, 2.032 g, 9.18 mmol) and THF (30 mL). The flask was cooled to −78° C. and lithium bis(trimethylsilyl)amide (1M in THF) (10.02 mL, 10.02 mmol) was added dropwise, rapidly. The flask was placed in an ice/water bath for 10 minutes, and then returned to −78° C., at which time a solution of 3-fluoro-4-nitrobenzenesulfonyl chloride (Matrix Scientific, Columbia, S.C., 2.000 g, 8.35 mmol) in THF (5 mL with a 1 mL wash) was added dropwise. After 15 minutes, the reaction was complete, and was quenched with aqueous saturated ammonium chloride solution. The mixture was warmed to RT and extracted with EtOAc. The organics were combined and dried over sodium sulfate, filtered and concentrated. The solids were taken up in methanol, and after triturating, were filtered and washed with methanol to yield 3-fluoro-N-(4-methoxybenzyl)-4-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide. (INTERMEDIATE I) (2.76 g, 6.50 mmol) as a light yellow solid. m/z (ESI) 446.7 (M+Na)+.

1. customreturned to −78° C., at which time
2. washwash)
3. additionwas added dropwise
4. waitAfter 15 minutes
5. customwas quenched with aqueous saturated ammonium chloride solution
6. temperatureThe mixture was warmed to RT
7. extractionextracted with EtOAc
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customafter triturating
12. filtrationwere filtered
13. washwashed with methanol