Phenyl chloroformate → Phenyl 5-cyano-3-(2-ethoxypyridin-3-yl)-2-oxo-3-[(phenoxycarbonyl)-oxy]indoline-1-carboxylate

HRID 1484614Notes

Reaction equation

HRID 1484614 reaction equation
Cl[C:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:3].[C:11]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17](=[O:22])[C:16]2([OH:32])[C:23]1[C:24]([O:29][CH2:30][CH3:31])=[N:25][CH:26]=[CH:27][CH:28]=1)#[N:12].ClCCl.[CH3:36][OH:37]>N1C=CC=CC=1>[C:11]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[N:18]([C:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:3])[C:17](=[O:22])[C:16]2([C:23]1[C:24]([O:29][CH2:30][CH3:31])=[N:25][CH:26]=[CH:27][CH:28]=1)[O:32][C:36]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:37])#[N:12]

Participants

5

Reactant 3

HCID 15891Phenyl chloroformateHCID 21226129Dichloromethane methanolHCID 670486385-Cyano-3-hydroxy-3-(2-ethoxypyridin-3-yl)-1,3-dihydroindol-2-one

Product 1

HCID 68572590Phenyl 5-cyano-3-(2-ethoxypyridin-3-yl)-2-oxo-3-[(phenoxycarbonyl)-oxy]indoline-1-carboxylateYield 87%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

4.63 ml (36.98 mmol) of phenyl chloroformate were slowly added dropwise, undiluted, at the preset temperature to a suspension, cooled to 0° C., of 5.20 g (17.61 mmol) of (±)-5-cyano-3-hydroxy-3-(2-ethoxypyridin-3-yl)-1,3-dihydroindol-2-one from example 1.2 in 100 ml of pyridine. After the reaction mixture had thawed to room temperature it was stirred for 2 hours. The progress of the reaction was followed by thin-layer chromatography (silica gel, dichloromethane/methanol 9:1). Excess pyridine was removed in vacuo, and the residue was poured into 200 ml of ice-water and extracted with ethyl acetate (3×). The organic phase was washed with water (2×). Traces of pyridine were still present in the phase. The organic phase was dried over sodium sulfate. After removal of the ethyl acetate in vacuo, the remaining pyridine was driven off by addition of toluene and removal in vacuo several times. The residue was dried under high vacuum. 8.20 g (15.31 mmol, 87%) of phenyl 5-cyano-3-(2-ethoxypyridin-3-yl)-2-oxo-3-[(phenoxycarbonyl)-oxy]indoline-1-carboxylate were obtained.

Workup

  1. customhad thawed to room temperature
  2. customExcess pyridine was removed in vacuo
  3. additionthe residue was poured into 200 ml of ice-water
  4. extractionextracted with ethyl acetate (3×)
  5. washThe organic phase was washed with water (2×)
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. customAfter removal of the ethyl acetate in vacuo
  8. additionthe remaining pyridine was driven off by addition of toluene and removal in vacuo several times
  9. customThe residue was dried under high vacuum

Sources & evidence

ORD record
ord-f9056230eecf4e93b1749f98567130bd
Source dataset
uspto-grants-2016_08
Patent number
US09422264B2

Reaction notes

Loading…