Sulfuric Acid → 2,6-Dichloro-5-fluoronicotinic acid
Reaction equation
[OH:1]C1C(C#N)=CC(F)=C(O)N=1.ClC1C(C#N)=CC(F)=C(Cl)N=1.P(Cl)(Cl)(Cl)=O.P(Cl)(Cl)(Cl)(Cl)Cl.[Cl:34][C:35]1[N:43]=[C:42]([Cl:44])[C:41]([F:45])=[CH:40][C:36]=1[C:37](N)=[O:38].S(=O)(=O)(O)O.N([O-])=O.[Na+]>>[Cl:34][C:35]1[N:43]=[C:42]([Cl:44])[C:41]([F:45])=[CH:40][C:36]=1[C:37]([OH:1])=[O:38]Participants
Reactant 7
Product 1
Procedure
A preferred embodiment for preparing the nicotinic acids is illustrated in Scheme II. The 2,6-dihydroxy-3-cyano-5-fluoropyridine (1) is prepared according to the method described in European Patent Application 333 020 (EP 020), incorporated herein by reference. This document describes the preparation of 2,6-dihydroxy-3-cyano-5-fluoropyridine starting with ethyl formate, ethyl fluoro acetate, and cyanoacetamide. The ethyl formate and ethyl fluoro acetate, are initially reacted in the presence of sodium methoxide, followed by addition of cyanoacetamide to provide the dihydroxy cyanopyridine (1). The 2,6-dihydroxy-3-cyano-5-fluoropyridine is converted to 2,6-dichloro-3-cyano-5-fluoropyridine (2) with phosphorus oxychloride (POCl3) and phosphorus pentachloride (PCl5). The 2,6-dichloro-5-fluoro-3-cyanopyridine is hydrolyzed to 2,6-dichloro-5-fluoronicotinamide (3) by heating the cyano compound in the presence of concentrated sulfuric acid. The 2,6-dichloro-5-fluoronicotinic acid (4) was prepared by reaction of the amide (3) with sodium nitrite under aqueous acidic conditions. ##STR8##
Sources & evidence
- ORD record
- ord-481c76475bdc404182bfc5611d652dbf
- Source dataset
- uspto-grants-1998_04
- Patent number
- US05739342
Reaction notes
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