Preparation method of 3-fluorophenylmethanesulfonyl chloride_Kain Industrial Additive

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