Dichloromethane → HCID 136005778, compound

HRID 915978Notes

Reaction equation

HRID 915978 reaction equation
ClCCl.C([N:11]1[CH2:16][CH2:15][CH:14]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[NH:25][C:26](=[O:40])[C:27]4[N:32]([CH:33]5[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]5)[N:31]=[C:30]([CH3:39])[C:28]=4[N:29]=3)=[C:20]([O:41][CH3:42])[CH:19]=2)[CH2:13][CH2:12]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O>ClCCCl>[CH:33]1([N:32]2[C:27]3[C:26](=[O:40])[NH:25][C:24]([C:21]4[CH:22]=[CH:23][C:18]([NH:17][CH:14]5[CH2:15][CH2:16][NH:11][CH2:12][CH2:13]5)=[CH:19][C:20]=4[O:41][CH3:42])=[N:29][C:28]=3[C:30]([CH3:39])=[N:31]2)[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38]1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 5213051-Chloroethyl chloroformate2×HCID 136005786HCID 136005786, compound

Product 1

HCID 136005778HCID 136005778, compoundYield 62.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a 3 ml dichloromethane solution of 120 mg (0.228 mmol) of the compound obtained in Example 223, 50 μl (0.456 mmol) of 1-chloroethyl chloroformate was added, and the mixture was stirred at room temperature for 4 hours. Further, 50 μl (0.456 mmol) of 1-chloroethyl chloroformate and 3 ml of 1,2-dichloroethane were added, and the mixture was heated under reflux for 5 hours. Then, the reaction mixture was distilled under reduced pressure, 3 ml of methanol was added to the residue, and the mixture was heated under reflux for 1.5 hours. The reaction mixture was cooled to room temperature, and the solvent was distilled off under reduced pressure. An aqueous solution of sodium hydrogen carbonate was added to the residue, and the mixture was extracted with dichloromethane. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate, whereafter the solvent was distilled off under reduced pressure. The residue was purified by basic silica gel column chromatography (dichloromethane/methanol=20/1) to obtain 62 mg (62%) of the captioned compound.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 5 hours
  3. distillationThen, the reaction mixture was distilled under reduced pressure, 3 ml of methanol
  4. additionwas added to the residue
  5. temperaturethe mixture was heated
  6. temperatureunder reflux for 1.5 hours
  7. temperatureThe reaction mixture was cooled to room temperature
  8. distillationthe solvent was distilled off under reduced pressure
  9. additionAn aqueous solution of sodium hydrogen carbonate was added to the residue
  10. extractionthe mixture was extracted with dichloromethane
  11. washThe organic layer was washed with water
  12. dry with materiala saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate, whereafter the solvent
  13. distillationwas distilled off under reduced pressure
  14. customThe residue was purified by basic silica gel column chromatography (dichloromethane/methanol=20/1)

Sources & evidence

ORD record
ord-e0ef6e8b92434036be92150ac6174216
Source dataset
uspto-grants-2007_09
Patent number
US07268128B2

Reaction notes

Loading…