Reaction #465978

Reaction equation

NaBH4

methyl 3-bromo-4,6-dichloropyridine-2-carboxylate

NaN3

H2O

H2O

→

4-amino-3-bromo-6-chloropyridine-2-carboxylic acid

Yield 27.3%

Solvents

DMF

MeOH

Conditions

Workup

1. 1
   Extractionextracted (3×) with Et2O
2. 2
   ConcentrationOrganic layer was concentrated
3. 3
   Otherto yield a white solid, which
4. 4
   Extractionextracted (3×) with Et2O
5. 5
   Dryingdried over MgSO4
6. 6
   Concentrationconcentrated
7. 7
   workup.STIRRINGThe resulting solid was stirred in 1N NaOH for 1 hr
8. 8
   Concentrationconcentrated to dryness
9. 9
   ExtractionThis material was extracted with MeOH
10. 10
    Concentrationconcentrated

Procedure

To a solution of methyl 3-bromo-4,6-dichloropyridine-2-carboxylate (0.9 g, 3.2 mmol) in aqueous DMF was added NaN3 (0.25 g, 3.8 mmol). The resulting mixture was heated at 60° C. for 1 hr, added to H2O and extracted (3×) with Et2O. Organic layer was concentrated to yield a white solid, which was dissolved in 10 mL of MeOH. Excess NaBH4 was added and the reaction mixture stirred at room temperature for 0.5 hr. This material was added to H2O, extracted (3×) with Et2O, dried over MgSO4 and concentrated. The resulting solid was stirred in 1N NaOH for 1 hr, made acidic with conc. HCl and concentrated to dryness. This material was extracted with MeOH, concentrated to give 220 mg of 4-amino-3-bromo-6-chloropyridine-2-carboxylic acid; mp 175° C. dec.

Source