Benzene → Methyl 2-bromo-5-fluoropyridine-4-carboxylate

HRID 1802180Notes

Reaction equation

HRID 1802180 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]([F:11])=[CH:9][N:10]=1)[C:5]([OH:7])=[O:6].[CH:12]1C=CC=CC=1>CO>[Br:1][C:2]1[CH:3]=[C:4]([C:8]([F:11])=[CH:9][N:10]=1)[C:5]([O:7][CH3:12])=[O:6]

Participants

4

Reactant 2

HCID 241BenzeneHCID 467392772-Bromo-5-fluoroisonicotinic acid

Product 1

HCID 46311206Methyl 2-bromo-5-fluoropyridine-4-carboxylateYield 88.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a cooled solution of 2-bromo-5-fluoroisonicotinic acid (3.0 g, 13.6 mmol) in benzene (20 ml) and methanol (10 ml) is dropwise over a period of 15 min added under stirring and cooling (trimethylsiliyl)diazomethane (2 M in ether, 14 ml, 28 mmol). The yellow solution is stirred for 1.5 h without cooling and evaporated to dryness. Purification of the residue (3.3 g) by chromatography on a 50 g Silicycle silica cartridge using a heptane/ethyl acetate 10-50% gradient affords methyl 2-bromo-5-fluoroisonicotinate (2.82 g, 88.4%) as a light yellow solid. mp.: 43-6° C. MS: m/z=233.9 (M+H+).

Workup

  1. additionadded
  2. stirringThe yellow solution is stirred for 1.5 h
  3. temperaturewithout cooling
  4. customevaporated to dryness
  5. customPurification of the residue (3.3 g) by chromatography on a 50 g Silicycle silica cartridge

Sources & evidence

ORD record
ord-33e90285f5d947f988114537a3c6efba
Source dataset
uspto-grants-2013_01
Patent number
US08349824B2

Reaction notes

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