Methanol → HCID 58996249, compound

HRID 1591575Notes

Reaction equation

HRID 1591575 reaction equation
[N-:1]=[N+]=[N-].[Na+].[Cl:5][C:6]1[C:7]([C:17]([O:19][CH3:20])=[O:18])=[N:8][C:9]([C:13]([F:16])([F:15])[CH3:14])=[CH:10][C:11]=1Cl.CO.[BH4-].[Na+]>CN(C)C=O.O>[NH2:1][C:11]1[CH:10]=[C:9]([C:13]([F:16])([F:15])[CH3:14])[N:8]=[C:7]([C:17]([O:19][CH3:20])=[O:18])[C:6]=1[Cl:5]

Participants

7

Reactant 4

HCID 887MethanolHCID 33557Sodium AzideHCID 4311764Sodium borohydrideHCID 58996246HCID 58996246, compound

Product 1

HCID 58996249HCID 58996249, compoundYield 56.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

Sodium azide (26.5 mg, 0.41 mmol) was added to a solution of methyl 3,4-dichloro-6-(1,1-difluroethyl)pyridine-2-carboxylate (100 mg, 0.37 mmol) in dimethylformamide (2 mL) and water (0.2 mL). After the reaction mixture was stirred at 50° C. for 5 hours, it was quenched with water and extracted with ethyl ether. The orgainc phase was dried and concentrated to provide the crude 4-azide compound. It was immediately taken up into methanol (2 mL) and sodium borohydride (21 mg, 0.55 mmol) was carefully added. After stirring for 10 minutes, water was added and the mixture concentrated. Ethyl acetate was added and the mixture washed with brine. The organic layer was dried (MgSO4), filtered and concentrated to dryness. The crude product was purified by column chromatography (20% ethyl acetate in hexane) to give methyl 4-amino-3-chloro-6-(1,1-difluroethyl)pyridine-2-carboxylate (53 mg, 0.21 mmol) as an oil; 1H NMR (CDCl3): δ 7.04 (s, 1H), 4.92 (b.s, 2H), 3.98 (s, 3H), 1.97 (t, d=18.7 Hz, 3H).

Workup

  1. customit was quenched with water
  2. extractionextracted with ethyl ether
  3. customThe orgainc phase was dried
  4. concentrationconcentrated
  5. customto provide the crude 4-azide compound
  6. additionwas carefully added
  7. stirringAfter stirring for 10 minutes
  8. concentrationthe mixture concentrated
  9. additionEthyl acetate was added
  10. washthe mixture washed with brine
  11. dry with materialThe organic layer was dried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated to dryness
  14. customThe crude product was purified by column chromatography (20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-d087a4f9f3de411496b8d0e9ce384ee2
Source dataset
uspto-grants-2007_11
Patent number
US07291580B2

Reaction notes

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