Thionyl Chloride → 4-Pyridinecarboxylic acid, 3-(chlorocarbonyl)-, methyl ester
Reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:10]([C:11]([OH:13])=O)=[CH:9][N:8]=[CH:7][CH:6]=1)=[O:4].S(Cl)([Cl:16])=O>>[CH3:1][O:2][C:3]([C:5]1[C:10]([C:11]([Cl:16])=[O:13])=[CH:9][N:8]=[CH:7][CH:6]=1)=[O:4]Participants
Procedure
Following the procedure of Example 30, 4-methoxycarbonylnicotinic acid is reacted with thionyl chloride to give 4-methoxycarbonylnicotinoyl chloride. A slurry of the above chloride (22.7 mmol) in 100 ml of monoglyme (ethylene glycol dimethyl ether) is added to a chilled mixture of the sodium salt of diethyl malonate (2.2 eq.) in monoglyme. The mixture is allowed to warm to RT and is stirred at RT for 4 hours. Aq. sodium bicarbonate is added and the mixture is extracted with ether. It is then acidified to pH 2-3 and again extracted with ether. The combined organic phases of the acid layer are dried, filtered and concentrated to give methyl 3-(diethylmalonyl-carbonyl)-isonicotinate, which is then reacted with lithium hydroxide mono-hydrate and then hydrochloric acid to give 3-acetylisonicotinic acid.
Sources & evidence
- ORD record
- ord-5275aa7c8b794dd2a30f7b3c3302bfbc
- Source dataset
- uspto-grants-1992_03
- Patent number
- US05098466
Reaction notes
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