Dichloromethane → HCID 90023961, compound

HRID 1484522Notes

Reaction equation

HRID 1484522 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=2)=[CH:4][C:3]=1[O:16][CH3:17].C(Cl)Cl.ClC(Cl)(O[C:25](=[O:31])OC(Cl)(Cl)Cl)Cl.C(N(CC)CC)C.[C:40]([NH:43][NH2:44])(=O)[CH3:41]>>[CH3:41][C:40]1[N:13]([C:12]2[CH:14]=[CH:15][C:9]([O:8][C:5]3[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([O:16][CH3:17])[CH:4]=3)=[CH:10][CH:11]=2)[C:25](=[O:31])[NH:44][N:43]=1

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 14039AcetohydrazideHCID 94429TriphosgeneHCID 67235564HCID 67235564, compound2×

Product 1

HCID 90023961HCID 90023961, compoundYield 82.1%

Procedure

To a solution of 4-{[4-methyl-3-(methyloxy)phenyl]oxy}aniline (Intermediate 11, 336 mg, 1.467 mmol) in DCM (50 mL) Triethylamine (296 mg, 2.93 mmol) was added followed by triphosgene (174 mg, 0.587 mmol). The reaction mixture was stirred at room temperature for 0.5 h. Triethylamine (296 mg, 2.93 mmol) and acetohydrazide (130 mg, 1.76 mmol) were then added and the reaction mixture was stirred at room temperature overnight. The solvent was concentrated in vacuum and the residue was dissolved in a 2M aqueous solution of NaOH (15 mL) and the mixture was heated to reflux for 12 h. The reaction mixture was neutralized with aqueous 6M HCl to pH=7 and extracted with DCM (3×50 mL). The combined organic phases were dried over Na2SO4 and concentrated under reduced pressure to give the crude product which was purified by flash chromatography on silica gel using dichloromethane/methanol as eluents from 100/1 to 50/1 to yield 150 mg of the title compound.

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. concentrationThe solvent was concentrated in vacuum
  3. dissolutionthe residue was dissolved in a 2M aqueous solution of NaOH (15 mL)
  4. temperaturethe mixture was heated
  5. temperatureto reflux for 12 h
  6. extractionextracted with DCM (3×50 mL)
  7. dry with materialThe combined organic phases were dried over Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customto give the crude product which
  10. customwas purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-907209f8247448fbbc2107281c55c8f4
Source dataset
uspto-grants-2016_08
Patent number
US09422252B2

Reaction notes

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