Tetrahydrofuran → 4-(4-Bromo-2-fluorophenylamino)-6-chloro-5-fluoro-nicotinic acid methyl ester

HRID 1971163Notes

Reaction equation

HRID 1971163 reaction equation
[CH3:1][Si](C=[N+]=[N-])(C)C.[Br:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:21]([C:22]([OH:24])=[O:23])=[CH:20][N:19]=[C:18]([Cl:25])[C:17]=2[F:26])=[C:11]([F:27])[CH:10]=1.C1COCC1>CO>[CH3:1][O:23][C:22](=[O:24])[C:21]1[C:16]([NH:15][C:12]2[CH:13]=[CH:14][C:9]([Br:8])=[CH:10][C:11]=2[F:27])=[C:17]([F:26])[C:18]([Cl:25])=[N:19][CH:20]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 167693TrimethylsilyldiazomethaneHCID 866015264-(4-Bromo-2-fluorophenylamino)-6-chloro-5-fluoro-nicotinic acid

Product 1

HCID 866015274-(4-Bromo-2-fluorophenylamino)-6-chloro-5-fluoro-nicotinic acid methyl esterYield 92.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A hexanes solution of TMSCH2N2 (9.46 mL, 18.9 mmol) was added to 4-(4-bromo-2-fluorophenylamino)-6-chloro-5-fluoro-nicotinic acid (4.59 g, 12.62 mmol) in a solution of 3:1 THF:MeOH (48 mL) at 0° C. The reaction mixture was warmed to room temperature and stirred for 1 hour. After quenching with AcOH, the reaction mixture was diluted with ethyl acetate and water. The layers were separated and the organic layer was washed with water, saturated NaHCO3 solution and brine. The organic layer was dried (MgSO4) and concentrated to give 4.40 g (92%) clean desired product.

Workup

  1. customat 0° C
  2. customAfter quenching with AcOH
  3. additionthe reaction mixture was diluted with ethyl acetate and water
  4. customThe layers were separated
  5. washthe organic layer was washed with water, saturated NaHCO3 solution and brine
  6. dry with materialThe organic layer was dried (MgSO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-87bf1e78b311448e96234623ba69a580
Source dataset
uspto-grants-2013_04
Patent number
US08431574B2

Reaction notes

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