background and overview[1]
3-fluorophenylmethanesulfonyl chloride can be used as a pharmaceutical synthesis intermediate. if 3-fluorophenylmethanesulfonyl chloride is inhaled, move the patient to fresh air; if the skin comes into contact, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical attention if you feel uncomfortable; if the eyes are clear in case of contact, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.
preparation[1]
3-fluorophenylmethanesulfonyl chloride can be used to prepare 3-fluoro-n-(1-((4-fluorophenyl)sulfonyl)-1,2,3,4-tetrahydroquinoline-7- base)benzenesulfonamide:
1) take 1,2,3,4-tetrahydroquinoline (2g), dissolve it in 20mldmf, place it in an ice bath, add 10mlh2so4 and slowly drop it into the mixture, react at 0℃ for 1 hour, then add 5 ml hno3, react at 0°c for 5 hours, add water, filter with suction, and wash with water twice to obtain a filter cake. ea/pe is recrystallized to obtain 1.9 g of product 7-nitro-1,2,3,4-tetrahydroquinoline.
2) take 7-nitro-1,2,3,4-tetrahydroquinoline (500mg), dissolve it in 10ml pyridine, place it at 100℃, add thiophene-2-sulfonyl chloride (762.6mg) add to the mixture, react at 100°c overnight, wash once with 10% hydrochloric acid, extract three times with ethyl acetate, combine the organic layers, wash once with saturated sodium chloride, dry over anhydrous sodium sulfate, and perform column chromatography with pe: ea to obtain 380 mg of product. .
3) take 1-((4-fluorophenyl)sulfonyl)-7-nitro-1,2,3,4-tetrahydroquinoline (300mg), dissolve it in 20ml methanol solution, and add 10 % palladium on carbon (30 mg) was added to the mixture, reacted at room temperature overnight, filtered with suction, spin off the solvent, and recrystallized ea/pe to obtain 220 mg of product.
4) take 1-((4-fluorophenyl)sulfonyl)-1,2,3,4-tetrahydroquinoline-7-amino (100mg), dissolve it in 10ml pyridine, place it in 100 ℃, add 3-fluorophenylmethanesulfonyl chloride (100mg) to the mixture, react at 100℃ overnight, wash once with 10% hydrochloric acid, extract three times with ethyl acetate, combine the organic layers, wash once with saturated sodium chloride, no dry over sodium sulfate and perform column chromatography with pe:ea to obtain 40 mg of product.
main reference materials
[1]cn201610064772.0 tetrahydroquinoline related bicyclic compounds and their applications
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