Hydrochloric Acid → Dimethyl (2,6-dichloropyridine-4-carbonyl)propanedioate

HRID 368927Notes

Reaction equation

HRID 368927 reaction equation
[Cl-].[Mg+2].[Cl-].[C:4]([O:11][CH3:12])(=[O:10])[CH2:5][C:6]([O:8][CH3:9])=[O:7].C(N(CC)CC)C.[Cl:20][C:21]1[CH:22]=[C:23]([CH:26]=[C:27]([Cl:29])[N:28]=1)[CH2:24]Cl.Cl.[OH2:31]>C(#N)C.ClCCl>[Cl:20][C:21]1[CH:22]=[C:23]([CH:26]=[C:27]([Cl:29])[N:28]=1)[C:24]([CH:5]([C:4]([O:11][CH3:12])=[O:10])[C:6]([O:8][CH3:9])=[O:7])=[O:31]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 962WaterHCID 7943Dimethyl malonateHCID 8471TriethylamineHCID 27946262,6-dichloro-4-(chloromethyl)pyridineHCID 5360315Magnesium Chloride

Product 1

HCID 22119448Dimethyl (2,6-dichloropyridine-4-carbonyl)propanedioateYield 89.2%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2312 g (24.28 mol) of magnesium chloride are introduced with cooling into 18 l of acetonitrile. After the exothermic reaction has subsided, the solution is cooled to 0° C. and 3210 g (24.3 mol) of dimethyl malonate are added dropwise with stirring in the course of 45 minutes. After this, 4920 g (48.62 mol) of triethylamine are added dropwise at 0° C. with stirring in the course of 1.5 hours. After addition is complete, the mixture is stirred at 0° C. for a further 15 minutes. A solution of 4742 g (22.53 mol) of 2,6-dichloro-isonicotinyl chloride in 6670 ml of acetonitrile is then added dropwise at 0° C. with stirring in the course of 20 hours. The mixture is first stirred for 1 hour at 0° C. and then for 16 hours while slowly warming to room temperature. 15.9 l of concentrated hydrochloric acid are then added dropwise with stirring to the reaction mixture with cooling to 0 to 10° C. After this, 15.9 l of dichloromethane and 6.4 l of water are added with stirring and the organic phase is then separated off. The aqueous phase is extracted once more with 7.9 l of dichloromethane. The combined organic phases are washed twice with 4 l of water each time and then concentrated under reduced pressure. The residue which remains is stirred with 9.5 l of water, then filtered off with suction and washed successively, first with 6.3 l of water and then twice with 7.9 l of petroleum ether each time. The product obtained is dried at 40° C. under reduced pressure. In this manner, 6.17 kg (89.2% of theory) of dimethyl 2,6-dichloro-isonicotinoyl-malonate are obtained.

Workup

  1. customAfter the exothermic reaction
  2. stirringwith stirring in the course of 1.5 hours
  3. additionAfter addition
  4. stirringthe mixture is stirred at 0° C. for a further 15 minutes
  5. stirringwith stirring in the course of 20 hours
  6. stirringThe mixture is first stirred for 1 hour at 0° C.
  7. temperaturefor 16 hours while slowly warming to room temperature
  8. stirringwith stirring to the reaction mixture
  9. temperaturewith cooling to 0 to 10° C
  10. stirringwith stirring
  11. customthe organic phase is then separated off
  12. extractionThe aqueous phase is extracted once more with 7.9 l of dichloromethane
  13. washThe combined organic phases are washed twice with 4 l of water each time
  14. concentrationconcentrated under reduced pressure
  15. stirringThe residue which remains is stirred with 9.5 l of water
  16. filtrationfiltered off with suction
  17. washwashed successively, first with 6.3 l of water
  18. customThe product obtained
  19. customis dried at 40° C. under reduced pressure

Sources & evidence

ORD record
ord-22440e8f48e943bebcf67988139a3886
Source dataset
uspto-grants-2000_10
Patent number
US06136754

Reaction notes

Loading…