Carbon Dioxide → 3-Chloromethylthio-7-fluoro-1-methyl-4-quinolone

HRID 1581768

Reaction equation

[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:16])[C:7]([S:13]([CH3:15])=O)=[CH:8][N:9]2[CH3:12])=[CH:4][CH:3]=1.S(Cl)([Cl:19])=O.N1C=CC=CC=1.C(=O)=O>CC(C)=O>[Cl:19][CH2:15][S:13][C:7]1[C:6](=[O:16])[C:5]2[C:10](=[CH:11][C:2]([F:1])=[CH:3][CH:4]=2)[N:9]([CH3:12])[CH:8]=1

Participants

Conditions

Temperature: -5 °C

Procedure

3.59 g (5 mmole) of racemic flosequinan (1) were added (over the course of one minute) to a mixture of thionyl chloride (12 ml) and pyridine (3 ml) with efficient stirring and gentle cooling in a bath of dry ice and acetone, to keep the temperature in the range of 0° C. to 6° C. The mixture was stirred at approximately 0° C. for 5 minutes, cooled to −5° C. and poured as a thin stream into 350 ml of ice-water with efficient stirring. After 10 minutes of stirring at 0° C., a solid was filtered off, washed with water and dried over phosphorous pentoxide, under high vacuum producing 2.82 g (74% yield) of 95% pure (by 1H NMR) 3-chloromethylthio-7-fluoro-1-methyl-4-quinolone (6). 1H NMR, CDCl3, δ=8.50 dd, 1H, J=6.6 & 9.0 Hz, H at C5; 8.01 s, 1H, H at C2; 7.18 ddd, 1H, J=2.1 & 9.0 & 10.2 Hz, H at C6; 7.09 dd, 1H, J=2.1 & 10.2 Hz, H at C8; 5.01 s, 2H, CH2; 3.83 s, 3H, N—CH3.

Workup

customin the range of 0° C. to 6° C
stirringThe mixture was stirred at approximately 0° C. for 5 minutes
stirringAfter 10 minutes of stirring at 0° C.
filtrationa solid was filtered off
washwashed with water
dry with materialdried over phosphorous pentoxide, under high vacuum

Sources & evidence

ORD record: ord-15967609aea44c4e93950d478e8aa6cc
Source dataset: uspto-grants-2004_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06730790B2

Linked notes

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