تفاعل #520139

معادلة التفاعل

(2R-trans)-1-[[[4-chloro-5-[[(chloromethyl)sulfonyl]amino]-2-fluorophenyl]amino]carbonyl]-4-fluoro-2-pyrrolidinecarboxylic acid

thionyl chloride

→

crude title compound

المردود 84.7%

(6S-cis)-1-chloro-N-[2-chloro-4-fluoro-5-(6-fluorotetrahydro-1,3-dioxo-1H-pyrrolo[1,2-c]imidazol-2(3H)-yl)phenyl]methanesulfonamide

المردود 84.7%

المذيبات

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   أخرىwas continued at room temperature
2. 2
   workup.WAITAfter 22 hours
3. 3
   أخرىthe layers were separated
4. 4
   استخلاصthe aqueous layer was extracted with dichloromethane (twice with 75 mL)
5. 5
   غسيلwashed with saturated aqueous sodium bicarbonate (twice with 400 mL),
6. 6
   تجفيفdried over magnesium sulfate
7. 7
   أخرىevaporated under reduced pressure

الإجراء التجريبي

Crude (2R-trans)-1-[[[4-chloro-5-[[(chloromethyl)sulfonyl]amino]-2-fluorophenyl]amino]carbonyl]-4-fluoro-2-pyrrolidinecarboxylic acid (173.43 g) was suspended in 550 mL of dichloromethane and 0.65 mL (0.61 g, 8.4 mmol) of N,N-dimethylformamide was added, followed by the dropwise addition of 58 mL (95 g, 0.80 mol) of thionyl chloride at room temperature, and stirring was continued at room temperature. After 2.5 hours, the mixture became homogeneous. After 22 hours, the mixture was poured into 500 mL of ice-water, the layers were separated and the aqueous layer was extracted with dichloromethane (twice with 75 mL). The organic layers were combined, washed with saturated aqueous sodium bicarbonate (twice with 400 mL), dried over magnesium sulfate and evaporated under reduced pressure to afford 140.69 g of the crude title compound (84.7% yield from the isocyanate).

المصدر