Phenyl chloroformate → 5-cyano-3-(2-ethoxypyridin-3-yl)-2-oxo-1-(phenylsulfonyl)-2,3-dihydro-1H-indol-3-yl phenyl carbonate

HRID 1484616Notes

Reaction equation

HRID 1484616 reaction equation
[CH2:1]([O:3][C:4]1[C:9]([C:10]2([OH:31])[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([C:19]#[N:20])[CH:17]=3)[N:12]([S:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)(=[O:23])=[O:22])[C:11]2=[O:30])=[CH:8][CH:7]=[CH:6][N:5]=1)[CH3:2].Cl[C:33]([O:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:34]>N1C=CC=CC=1.ClCCl>[C:33](=[O:34])([O:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[O:31][C:10]1([C:9]2[C:4]([O:3][CH2:1][CH3:2])=[N:5][CH:6]=[CH:7][CH:8]=2)[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:19]#[N:20])[CH:17]=2)[N:12]([S:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)(=[O:23])=[O:22])[C:11]1=[O:30]

Participants

5

Reactant 2

HCID 15891Phenyl chloroformateHCID 685568513-(2-Ethoxypyridin-3-yl)-3-hydroxy-2-oxo-1-(phenylsulfonyl)indoline-5-carbonitrile

Product 1

HCID 698117605-cyano-3-(2-ethoxypyridin-3-yl)-2-oxo-1-(phenylsulfonyl)-2,3-dihydro-1H-indol-3-yl phenyl carbonate

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

2.65 g (6.09 mmol) of optically active 3-(2-ethoxypyridin-3-yl)-3-hydroxy-2-oxo-1-(phenylsulfonyl)indoline-5-carbonitrile from example 4B.1 were dissolved in 4.9 ml of pyridine and 6.0 ml of dichloromethane while cooling at 0° C. in ice, the solution becoming brown in color. At this temperature, 1.24 g (7.91 mmol) of phenyl chloroformate were slowly added dropwise. The reaction mixture was stirred in an ice bath for 2 hours. After conversion was complete, the reaction mixture was further diluted with dichloromethane and poured into ice-water. The phases were separated, and the organic phase was washed again with saturated sodium chloride solution (1×) and water (1×). The solvent was evaporated in vacuo, and excess pyridine was removed by codistillation with toluene. 50 ml of diisopropyl ether were added to precipitate the product, and, after the solid had been filtered off with suction and washed with diisopropyl ether, a total of 2.16 g (3.89 mmol, 64%) of the optically active 5-cyano-3-(2-ethoxypyridin-3-yl)-2-oxo-1-(phenylsulfonyl)-2,3-dihydro-1H-indol-3-yl phenyl carbonate was isolated. Further purification of the mother liquor by normal-phase chromatography with dichloromethane as mobile phase resulted in 800 mg of the optically active 5-cyano-3-(2-ethoxypyridin-3-yl)-2-oxo-1-(phenylsulfonyl)-2,3-dihydro-1H-indol-3-ylphenyl carbonate.

Workup

  1. customThe phases were separated
  2. washthe organic phase was washed again with saturated sodium chloride solution (1×) and water (1×)
  3. customThe solvent was evaporated in vacuo, and excess pyridine
  4. customwas removed by codistillation with toluene
  5. addition50 ml of diisopropyl ether were added
  6. customto precipitate the product
  7. filtrationafter the solid had been filtered off with suction
  8. washwashed with diisopropyl ether

Sources & evidence

ORD record
ord-13df32e5ec6947569e132919982e54c3
Source dataset
uspto-grants-2016_08
Patent number
US09422264B2

Reaction notes

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