Reaction #2200597

Reaction equation

lithium hydroxide

methyl 4-amino-3-chloro-6-ethyl-5-fluoropyridine-2-carboxylate

→

4-amino-3-chloro-6-ethyl-5-fluoropyridine-2-carboxylic acid

Yield 78.5%

Solvents

water

tetrahydrofuran

Conditions

Workup

1. 1
   Concentrationwas then concentrated to half volume
2. 2
   workup.ADDITIONAfter adding water the reaction mixture
3. 3
   Washwas washed once with ethyl acetate
4. 4
   Otherto remove unreacted
5. 5
   Concentrationconcentrated
6. 6
   Otherthe residue partitioned between tetrahydrofuran and brine
7. 7
   Concentrationthe organic layer concentrated
8. 8
   Otherdried under vacuum

Procedure

A solution of lithium hydroxide (0.49 g, 11.73 mmol) in water (25 mL) was added to a solution of methyl 4-amino-3-chloro-6-ethyl-5-fluoropyridine-2-carboxylate (1.36 g, 5.86 mmol) in tetrahydrofuran (25 mL). The mixture was vigorously stirred at room temperature overnight and was then concentrated to half volume. After adding water the reaction mixture was washed once with ethyl acetate to remove unreacted starting material. The aqueous layer was then acidified to pH<3 with 1N HCl, concentrated and the residue partitioned between tetrahydrofuran and brine. The aqueous layer was discarded and the organic layer concentrated and dried under vacuum to provide 4-amino-3-chloro-6-ethyl-5-fluoropyridine-2-carboxylic acid (1.01 g, 4.60 mmol) as a white solid, mp 144-145° C.

Source