Oxalyl chloride → 6-Chloro-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

HRID 1500692Notes

Reaction equation

HRID 1500692 reaction equation
[Cl:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([Si:19]([CH3:22])([CH3:21])[CH3:20])=[CH:15][C:14]=2[F:23])[N:3]=1.[C:24](Cl)(=O)C(Cl)=O>ClCCl.CN(C=O)C>[CH3:24][O:7][C:6](=[O:8])[C:5]1[CH:9]=[C:10]([F:11])[C:2]([Cl:1])=[N:3][C:4]=1[NH:12][C:13]1[CH:18]=[CH:17][C:16]([Si:19]([CH3:20])([CH3:22])[CH3:21])=[CH:15][C:14]=1[F:23]

Participants

5

Reactant 2

HCID 65578Oxalyl chlorideHCID 591401336-Chloro-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid

Product 1

HCID 591401696-Chloro-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl esterYield 92.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 6-chloro-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid (7.6 g, 21.3 mmol) in dichloromethane (100 mL) and DMF (1 mL) was added oxalyl chloride (9.1 mL, 106.4 mmol) dropwise over 20 minutes. The reaction mixture was stirred at reflux for 18 hours and then concentrated in vacuo and the residue azeotroped with toluene. The resultant residue was taken up in cold (0° C.) methanol (100 mL). The resultant solution was heated at reflux for 1 hour, then cooled to room temperature and filtered. The precipitate was washed with cold methanol and dried under vacuum at 45° C. to give the title compound as a yellow solid (7.3 g, 92%). LCMS (method B): RT=5.38 min, [M+H]+=371.

Workup

  1. temperatureat reflux for 18 hours
  2. concentrationconcentrated in vacuo
  3. customthe residue azeotroped with toluene
  4. customwas taken up in cold (0° C.) methanol (100 mL)
  5. temperatureThe resultant solution was heated
  6. temperatureat reflux for 1 hour
  7. filtrationfiltered
  8. washThe precipitate was washed with cold methanol
  9. customdried under vacuum at 45° C.

Sources & evidence

ORD record
ord-afda34a947624489a3640730663a00d7
Source dataset
uspto-grants-2015_12
Patent number
US09206174B2

Reaction notes

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