Thionyl Chloride → 3-Dichloromethylthio-7-fluoro-1-methyl-4-quinolone

Participants

Reaction Conditions

Reaction Steps

To an efficiently stirred and gently cooled 4.2 ml mixture of thionyl chloride (“SOCl2”) and 1.05 ml of pyridine (“Py”) at −3° C. was added 1.015 g (3.708 mmol) of 3-chloromethylsulfinyl-7-fluoro-1-methyl-4-quinolone (monochloroflosequinan)(Compound 1 of FIG. 21). This addition was made in multiple alloquots over a period of approximately 1 min. During this addition, cooling was applied to keep the temperature in the range 0-5° C. This mixture was then stirred at 0° C. for 8 min and then cooled to −5° C. The mixture was then poured as a thin stream into, stirring, 120 ml of ice-water. After 10 minutes of stirring at 0° C., a solid was filtered off, washed with water, and dried over phosphorus pentoxide under high vacuum. [Yield: 669 mg (61.7%) of a crude product (i.e. Compound 2) that was approximately 94% pure by 1H NMR, CDCl3; d=3.84 s, 3H, N—CH3; 7.11 dd, 1H, J=10.0 & 2.2 Hz, H at C8, 7.19 ddd, 1H, J=8.9, 7.9 & 2.3 Hz, H at C6; 7.24 s, 1H, CHCl2; 8.03 s, 1H, H at C2; 8.47 dd, 1H, J=9.0 & 6.3 Hz, H at C5.]. This product was then, further, purified in Step B described below.

Provenance & Evidence