Lithium Hydroxide → 4-Amino-3-chloro-6-ethyl-5-fluoropyridine-2-carboxylic acid

HRID 2113415Notes

Reaction equation

HRID 2113415 reaction equation
[OH-].[Li+].[NH2:3][C:4]1[C:9]([F:10])=[C:8]([CH2:11][CH3:12])[N:7]=[C:6]([C:13]([O:15]C)=[O:14])[C:5]=1[Cl:17]>O.O1CCCC1>[NH2:3][C:4]1[C:9]([F:10])=[C:8]([CH2:11][CH3:12])[N:7]=[C:6]([C:13]([OH:15])=[O:14])[C:5]=1[Cl:17]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 67026614Methyl 4-amino-3-chloro-6-ethyl-5-fluoropyridine-2-carboxylate

Product 1

HCID 670266094-Amino-3-chloro-6-ethyl-5-fluoropyridine-2-carboxylic acidYield 78.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

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.

Workup

  1. concentrationwas then concentrated to half volume
  2. additionAfter adding water the reaction mixture
  3. washwas washed once with ethyl acetate
  4. customto remove unreacted
  5. concentrationconcentrated
  6. customthe residue partitioned between tetrahydrofuran and brine
  7. concentrationthe organic layer concentrated
  8. customdried under vacuum

Sources & evidence

ORD record
ord-447f19aa406c428fbf8a92b64913814b
Source dataset
uspto-grants-2008_10
Patent number
US07432227B2

Reaction notes

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