m-Chloroperbenzoic acid → 3-Dichloromethylsulfinyl-7-fluoro-1-methyl-4-quinolone

665 mg (2.276 mmol) of the 3-dichloromethylthio-7-fluoro-1-methyl-4-quinolone (Compound 2, FIG. 1), as prepared in Step A, was dissolved in 20 ml of DCM at 0° C. to form a solution. To this solution was added 505.7 mg (2.345 mmol) of 80% MCPBA to form a mixture. This stirred mixture was then allowed to warm to room temperature and was stirred for 1 hour. An additional 25 mg of MCPBA was added and the mixture and stirred for 1 hour. The mixture was washed with 5% aqueous Na2CO3. The aqueous layer was extracted with DCM, and the combined DCM extracts were dried over anhydrous Na2SO4 and concentrated. The residue was chromatographed on silica gel with hexane-ethyl acetate (gradient 4:1,2:1,1:1) to give 352 mg (50%) of the product (Compound 3, FIG. 1) as a white solid, that was approximately 98% pure according to 1H NMR, CDCl3; d=3.96 s, 3H, N—CH3; 7.09 s, 1H, CHCl2; 7.22 dd, 1H, J=10.2 & 2.4 Hz, H at C8, 7.27 ddd, 1H, J=9.0, 7.6 & 2.2 Hz, H at C6; 8.03 s, 1H, H at C2; 8.43 dd, 1H, J=8.8 & 6.1 Hz, H at C5. This white solid product was further purified by recrystallization from methanol to give 252 mg of white crystals.

1. customto form a solution
2. customto form a mixture
3. stirringthe mixture and stirred for 1 hour
4. washThe mixture was washed with 5% aqueous Na2CO3
5. extractionThe aqueous layer was extracted with DCM
6. dry with materialthe combined DCM extracts were dried over anhydrous Na2SO4
7. concentrationconcentrated
8. customThe residue was chromatographed on silica gel with hexane-ethyl acetate (gradient 4:1,2:1,1:1)

ORD record

ord-a0cea175b54f4eb4b41999ecc8575966

Source dataset

uspto-grants-2004_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06835836B2