[F:1][CH2:2][C:3]([O:5]CC)=O.[CH:8](OCC)=O.C[O-].[Na+].[C:16]([O:22][CH3:23])(=[O:21])[CH2:17][C:18]([NH2:20])=[O:19].Cl>CO.O>[OH:19][C:18]1[N:20]=[C:3]([OH:5])[C:2]([F:1])=[CH:8][C:17]=1[C:16]([O:22][CH3:23])=[O:21]
To a solution of ethyl fluoroacetate (34 g) and ethyl formate (28 g) at 0° C. is added sodium methoxide (26 g). After 3.5 hours at 20° C., a solution of methyl malonamate (40 g) in methanol (350 mL) is added and the mixture heated at reflux for 0.5 hour. To the hot mixture is added a solution of 37% hydrochloric acid (48 mL) in water (352 mL). The reaction mixture is heated at reflux for 10 minutes. After standing at 0° C. for 18 hours, the mixture is filtered and the collected solid is washed with 3 to 400 mL of water and then vacuum dried to give methyl 2,6-dihydroxy-5-fluoronicotinate, (36.6 g, 61%): mp 208°-213° C.; HPLC 95.4%.
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