Hydrochloric Acid → HCID 57105160, compound

HRID 1060183Notes

Reaction equation

HRID 1060183 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].[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22]Cl)=[CH:18][C:17]=1[Cl:24].Cl>C1COCC1.CCOCC.C(Cl)Cl>[Cl:24][C:17]1[CH:18]=[C:19]([CH2:22][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:20]=[CH:21][C:16]=1[Cl:15]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 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 12 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. additionSome 12 was added
  6. temperatureat reflux temperature
  7. customThe Grignard-reagent was decanted off
  8. additionadded to mixture I at <−40° C.
  9. customthe resulting reaction mixture
  10. stirringwas stirred
  11. customto reach RT
  12. stirringThe reaction mixture was stirred for one hour at RT
  13. stirringthe mixture was stirred for 30 minutes
  14. customThe organic layer was separated
  15. customdried
  16. filtrationfiltered
  17. customthe solvent evaporated

Sources & evidence

ORD record
ord-c4f3e131b9fd4cc2b08415b7f011fb43
Source dataset
uspto-grants-2003_02
Patent number
US06521621B1

Reaction notes

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