Water → HCID 21696670, compound

HRID 378778Notes

Reaction equation

HRID 378778 reaction equation
[N-:1]=[N+]=[N-].[Na+].[Cl:5][C:6]1[C:7]([C:14]([O:16][CH3:17])=[O:15])=[N:8][C:9]([F:13])=[CH:10][C:11]=1F.O>CN(C)C=O>[NH2:1][C:11]1[CH:10]=[C:9]([F:13])[N:8]=[C:7]([C:14]([O:16][CH3:17])=[O:15])[C:6]=1[Cl:5]

Participants

5

Reactant 3

HCID 962WaterHCID 33557Sodium AzideHCID 21696658HCID 21696658, compound

Product 1

HCID 21696670HCID 21696670, compoundYield 81.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium azide (0.0086 mol, 0.60 g) was added to a solution of methyl 3-chloro-4,6-difluoropyridine-2-carboxylate (0.0072 mol, 1.5 g) in 15 mL dimethyl formamide (DMF). The solution was stirred 10 min at ambient temperature before pouring into 350 mL water and extracting the aqueous mixture with EtOAc (2×100 mL). The organic phase was dried (Na2SO4) and then treated with excess NaBH4 for 30 min. The excess NaBH4 was quenched with aqueous EtOH and the mixture was diluted with water (200 mL). The organic layer was separated and the aqueous layer extracted with EtOAc (2×200 mL). The combined organic layers were dried (Na2SO4) and concentrated to an off-white powder which was purified by reversed-phase HPLC to give methyl 4-amino-3-chloro-6-fluoropyridine-2-carboxylate (0.0059 mol, 1.2 g). 1H NMR(CDCl3): δ 3.95 (3H, s), 5.2-5.1 (2H, bs), 6.36 (1H, s). 19F NMR {1H}: δ −72.7.

Workup

  1. extractionextracting the aqueous mixture with EtOAc (2×100 mL)
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. additiontreated with excess NaBH4 for 30 min
  4. customThe excess NaBH4 was quenched with aqueous EtOH
  5. additionthe mixture was diluted with water (200 mL)
  6. customThe organic layer was separated
  7. extractionthe aqueous layer extracted with EtOAc (2×200 mL)
  8. dry with materialThe combined organic layers were dried (Na2SO4)
  9. concentrationconcentrated to an off-white powder which
  10. customwas purified by reversed-phase HPLC

Sources & evidence

ORD record
ord-e6c88da9fc2f4f59bff4d3328a36a370
Source dataset
uspto-grants-2001_10
Patent number
US06297197B1

Reaction notes

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