Reaction #44223

Reaction equation

2-(4-bromo-2-fluorophenylamino)-6-chloronicotinic acid methyl ester

2-(4-bromo-2-fluorophenylamino)-6-chloronicotinic acid

(trimethylsilyl)diazomethane

→

pure desired product

Yield 93.0%

2-(4-Bromo-2-fluorophenylamino)-6-oxo-1,6-dihydropyridine-3-carboxylic acid

Yield 93.0%

Solvents

methanol benzene

Conditions

Workup

1. 1
   OtherSolids precipitated out of solution
2. 2
   OtherExcess (trimethylsilyl)diazomethane was quenched by the dropwise addition of glacial acetic acid
3. 3
   FiltrationThe precipitated solids were filtered
4. 4
   Washwashed with methanol
5. 5
   ConcentrationThe filtrate was concentrated to a smaller volume and additional solids
6. 6
   Otherprecipitated out of solution that
7. 7
   Filtrationwere filtered
8. 8
   Washwashed with methanol
9. 9
   Otherdried under vacuum

Procedure

Preparation of 2-(4-bromo-2-fluorophenylamino)-6-chloronicotinic acid methyl ester: To a suspension of 2-(4-bromo-2-fluorophenylamino)-6-chloronicotinic acid (5.00 g, 14.5 mmol) in methanol/benzene (1:1, 100 mL) under N2 was added (trimethylsilyl)diazomethane (2.0 M solution in hexanes) dropwise until the bubbling caused by gas evolution ceased. Solids precipitated out of solution. The reaction was allowed to stir for 1 hour. Excess (trimethylsilyl)diazomethane was quenched by the dropwise addition of glacial acetic acid. The precipitated solids were filtered and washed with methanol. The filtrate was concentrated to a smaller volume and additional solids precipitated out of solution that were filtered and washed with methanol. The solids were combined and dried under vacuum to yield 4.82 g (93%) of pure desired product as a dark pink solid.

Source