Ethyl chloroformate → HCID 135621737, compound

HRID 1783317Notes

Reaction equation

HRID 1783317 reaction equation
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[O:18][N:17]=[C:16]([CH:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:21][CH2:20]2)[C:15]=1[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.NC1ON=C(C2CCN(C(OC)=O)CC2)C=1C1C=CC=CC=1.[Cl-].[Al+3].[Cl-].[Cl-].C(=O)([O-])[O-].[K+].[K+].ClC(OCC)=O>C(Cl)Cl.N1C=CC=CC=1>[CH2:28]([O:27][C:25]([N:22]1[CH2:23][CH2:24][CH:19]([C:16]2[C:15]3[C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][C:35]=4[C:2](=[O:4])[NH:13][C:14]=3[O:18][N:17]=2)[CH2:20][CH2:21]1)=[O:26])[CH3:29]

Participants

9

Reactant 6

HCID 10928Ethyl chloroformateHCID 11430Potassium CarbonateHCID 94429TriphosgeneHCID 6451240Aluminum(III) ChlorideHCID 23084685HCID 23084685, compoundHCID 23084750HCID 23084750, compound

Product 1

HCID 135621737HCID 135621737, compoundYield 130.2%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

Triphosgene (1.83 g) was dissolved in methylene chloride (20 mL), a solution (30 mL) of a mixture (1:1, 5.57 g) of 5-amino-3-(1-ethoxycarbonylpiperidin-4-yl)-4-phenylisoxazole and 5-amino-3-(1-methoxycarbonylpiperidin-4-yl)-4-phenylisoxazole, and pyridine (3.50 g) in methylene chloride was added dropwise under ice-cooling. After the completion of the dropwise addition, the mixture was stirred under ice-cooling for 20 min, and then at room temperature for 6.5 hrs. The reaction mixture was ice-cooled, aluminum chloride (16.7 g) was added, and the mixture was stirred overnight at room temperature. After the completion of the reaction, the reaction mixture was poured into ice-water, and potassium carbonate was added to alkalify the reaction mixture. An excess amount of ethyl chloroformate was added to the reaction mixture, and the mixture was stirred at room temperature. The insoluble material was filtered off through celite, and the aqueous layer was extracted with chloroform. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The precipitated crystals were collected by filtration with diethyl ether and a small amount of methanol to give a mixture (1:1, 2.74 g) of 1-(1-ethoxycarbonylpiperidin-4-yl)-isoxazolo[5,4-c]isoquinolin-5(4H)-one and 1-(1-methoxycarbonylpiperidin-4-yl)-isoxazolo[5,4-c]isoquinolin-5(4H)-one as colorless crystals.

Workup

  1. temperaturecooling
  2. additionAfter the completion of the dropwise addition
  3. temperaturecooling for 20 min
  4. temperaturecooled
  5. stirringthe mixture was stirred overnight at room temperature
  6. customAfter the completion of the reaction
  7. additionwas added
  8. stirringthe mixture was stirred at room temperature
  9. filtrationThe insoluble material was filtered off through celite
  10. extractionthe aqueous layer was extracted with chloroform
  11. dry with materialThe organic layer was dried over magnesium sulfate
  12. customthe solvent was evaporated under reduced pressure
  13. filtrationThe precipitated crystals were collected by filtration with diethyl ether

Sources & evidence

ORD record
ord-2b21e90475f348b6afa0c3c727bba012
Source dataset
uspto-grants-2009_03
Patent number
US07501412B2

Reaction notes

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