Selectfluor → Methyl 6-amino-5-bromo-3-fluoropicolinate

HRID 970383Notes

Reaction equation

HRID 970383 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][C:3]=1[Br:12].[F:13][B-](F)(F)F.F[B-](F)(F)F.ClC[N+]12CC[N+](F)(CC1)CC2>C(#N)C>[NH2:1][C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[C:5]([F:13])=[CH:4][C:3]=1[Br:12]

Participants

4

Reactant 2

HCID 2724933SelectfluorHCID 10704661Methyl 6-amino-5-bromopicolinate

Product 1

HCID 21873678Methyl 6-amino-5-bromo-3-fluoropicolinate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of methyl 6-amino-5-bromopyridine-2-carboxylate (19.8 g) (T. R. Kelly and F. Lang, J. Org. Chem. 61, 1996, 4623-4633) and 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (34.3 g) in acetonitrile (340 mL) under argon was heated to 40° C. for 1 hour, 60° C. for 1 hour and then 80° C. overnight. After partitioning between EtOAc and water (500 mL each) the aqueous fraction was re-extracted with EtOAc (300 mL) and the combined organic solution dried with MgSO4 and evaporated. Chromatography (20% then 30% EtOAc in hexane) separated various byproducts from the required ester (2.09 g).

Workup

  1. custom80° C. overnight
  2. customAfter partitioning between EtOAc and water (500 mL each) the aqueous fraction
  3. extractionwas re-extracted with EtOAc (300 mL)
  4. dry with materialthe combined organic solution dried with MgSO4
  5. customevaporated
  6. customChromatography (20% then 30% EtOAc in hexane) separated various byproducts from the required ester (2.09 g)

Sources & evidence

ORD record
ord-32a051ceab1e463dbfef031cd5240b8e
Source dataset
uspto-grants-2007_12
Patent number
US07312212B2

Reaction notes

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