Methanol → Methyl 6-chloro-5-nitronicotinate

HRID 453275Notes

Reaction equation

HRID 453275 reaction equation
CN([CH:4]=[O:5])C.O[C:7]1[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][C:10](C(O)=O)=[CH:9][N:8]=1.O=S(Cl)[Cl:21].[CH3:23][OH:24].C([O-])(O)=O.[Na+]>>[Cl:21][C:7]1[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][C:10]([C:23]([O:5][CH3:4])=[O:24])=[CH:9][N:8]=1

Participants

6

Reactant 5

HCID 887MethanolHCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 178524776HCID 178524776, compound

Product 1

HCID 346961Methyl 6-chloro-5-nitronicotinateYield 90%

Conditions

Temperature
-40 °C

Procedure

DMF (0.15 eq) was added to a solution of 6-hydroxy-5-nitronicotinic acid (1 eq) in SOCl2 (4.7 eq). The mixture was heated at reflux for 8 h then concentrated in vacuo. The residue was taken up in CH2Cl2, cooled to −40° C., and MeOH (1.4 eq) added while maintaining the internal temperature below −30° C. Aqueous NaHCO3 (1 eq) was added and the mixture allowed to warm to room temperature. The organic phase was separated and concentrated in vacuo. The crude residue was crystallized from EtOH to give methyl 6-chloro-5-nitronicotinate (90% yield)

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 8 h
  3. concentrationthen concentrated in vacuo
  4. temperaturewhile maintaining the internal temperature below −30° C
  5. temperatureto warm to room temperature
  6. customThe organic phase was separated
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was crystallized from EtOH

Sources & evidence

ORD record
ord-e58c954377164105a40bc6351c97cb54
Source dataset
uspto-grants-2013_07
Patent number
US08492401B2

Reaction notes

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