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 & 22 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-Eintrag

ord-c945b9e8765344c8b57ff62707117bd9

Quelldatensatz

uspto-grants-2006_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07045627B2