Phenyl chloroformate → Phenyl 5-cyano-3-(2-ethoxypyridin-3-yl)-6-fluoro-2-oxo-3-phenoxycarbonyloxy-2,3-dihydroindole-1-carboxylate

HRID 57198Notes

Reaction equation

HRID 57198 reaction equation
Cl[C:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:3].[CH2:11]([O:13][C:14]1[C:19]([C:20]2([OH:33])[C:28]3[C:23](=[CH:24][C:25]([F:31])=[C:26]([C:29]#[N:30])[CH:27]=3)[NH:22][C:21]2=[O:32])=[CH:18][CH:17]=[CH:16][N:15]=1)[CH3:12]>N1C=CC=CC=1.ClCCl>[C:29]([C:26]1[CH:27]=[C:28]2[C:23](=[CH:24][C:25]=1[F:31])[N:22]([C:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:3])[C:21](=[O:32])[C:20]2([C:19]1[C:14]([O:13][CH2:11][CH3:12])=[N:15][CH:16]=[CH:17][CH:18]=1)[O:33][C:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:3])#[N:30]

Participants

5

Reactant 2

HCID 15891Phenyl chloroformateHCID 670874583-(2-ethoxypyridin-3-yl)-6-fluoro-3-hydroxy-2-oxo-2,3-dihydro-1H-indole-5-carbonitrile

Product 1

HCID 67087492Phenyl 5-cyano-3-(2-ethoxypyridin-3-yl)-6-fluoro-2-oxo-3-phenoxycarbonyloxy-2,3-dihydroindole-1-carboxylateYield 79.7%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

330 μl (2.62 mmol) of phenyl chloroformate were slowly added dropwise to a solution, cooled to 0° C., of 342 mg (0.66 mmol; 60% purity) of 3-(2-ethoxypyridin-3-yl)-6-fluoro-3-hydroxy-2-oxo-2,3-dihydro-1H-indole-5-carbonitrile (mother liquor from example a.2) in 8 ml of pyridine, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane and extracted with water. The organic phase was washed with water and saturated sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (Redisep cartridge, mobile phase gradient from 0 to 5% methanol in dichloromethane). 291 mg of the title compound were obtained.

Workup

  1. extractionextracted with water
  2. washThe organic phase was washed with water and saturated sodium chloride solution
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by chromatography on silica gel (Redisep cartridge, mobile phase gradient from 0 to 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-13f7a9ccf69f4dcc9a051cfa57b5a377
Source dataset
uspto-grants-2016_09
Patent number
US09434713B2

Reaction notes

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