Hydrochloric Acid → HCID 57105160, compound

HRID 1530919Notes

Reaction equation

HRID 1530919 reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.Cl[C:10]([O:12][CH2:13][CH3:14])=[O:11].II.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24]Cl)=[CH:20][C:19]=1[Cl:26].Cl>C1COCC1.CCOCC.C(Cl)Cl>[Cl:26][C:19]1[CH:20]=[C:21]([CH2:24][C:5]2[N:6]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:7][CH2:8][C:3](=[O:2])[CH:4]=2)[CH:22]=[CH:23][C:18]=1[Cl:17]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 807IodineHCID 76093,4-Dichlorobenzyl chloride2×HCID 10928Ethyl chloroformateHCID 692784-Methoxypyridine

Product 1

HCID 57105160HCID 57105160, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-methoxypyridine (0.4 mol) in THF (1000 ml) was stirred and cooled in a 2-propanol/CO2 bath. Ethyl chloroformate (0.4 mol) was added dropwise and the mixture was stirred for 3 hours while cooling (mixture I). In another round-bottom flask, the Grignard-reagent was prepared: MG (0.44 mol) was stirred in a small amount of (C2H5)2O. Some I2 was added. A small amount of 1,2-dichloro-4-(chloromethyl)benzene was added. Then, 1,2-dichloro-4-(chloromethyl)benzene (0.4 mol) in (C2H5)2O (600 ml) was added dropwise at reflux temperature. The mixture was stirred for one hour (mixture II). The Grignard-reagent was decanted off, added to mixture I at <−40° C., and the resulting reaction mixture was stirred, allowing the temperature to reach RT. The reaction mixture was stirred for one hour at RT. HCl (10%, 800 ml) was added and the mixture was stirred for 30 minutes, then CH2Cl2 was added. The organic layer was separated, dried, filtered and the solvent evaporated, yielding 57.8 g (44%) of (±)-ethyl 6-[(3,4-dichlorophenyl)methyl]-1,2,3,4-tetrahydro-4-oxo-1-pyridinecarboxylate (intermediate 9).

Workup

  1. temperaturecooled in a 2-propanol/CO2 bath
  2. stirringthe mixture was stirred for 3 hours
  3. temperaturewhile cooling (mixture I)
  4. customIn another round-bottom flask, the Grignard-reagent was prepared
  5. temperatureat reflux temperature
  6. customThe Grignard-reagent was decanted off
  7. additionadded to mixture I at <−40° C.
  8. customthe resulting reaction mixture
  9. stirringwas stirred
  10. customto reach RT
  11. stirringThe reaction mixture was stirred for one hour at RT
  12. stirringthe mixture was stirred for 30 minutes
  13. customThe organic layer was separated
  14. customdried
  15. filtrationfiltered
  16. customthe solvent evaporated

Sources & evidence

ORD record
ord-86449ec7fff34b658cc02db7bbec423d
Source dataset
uspto-grants-2001_03
Patent number
US06197772B1

Reaction notes

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