Methanol → Methyl 5-bromo-2-chloronicotinate

HRID 533144Notes

Reaction equation

HRID 533144 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5]([Cl:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].OS(O)(=O)=O.[CH3:17]O>>[CH3:17][O:8][C:7](=[O:9])[C:6]1[CH:10]=[C:2]([Br:1])[CH:3]=[N:4][C:5]=1[Cl:11]

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 27633425-Bromo-2-chloronicotinic acid

Product 1

HCID 2763343Methyl 5-bromo-2-chloronicotinate

Conditions

Temperature
60 °C

Procedure

To 0.5 L flask charged with 5-Bromo-2-chloronicotinic acid (25.0 g, 106.4 mmol) in MeOH (250 mL) was added H2SO4 (5 mL). The mixture was heated to 60° C., stirred for 1.5 day. LC-MS indicated full conversion of starting material at this time. The reaction was cooled to RT and the volatile components removed in vacuo. The crude residue was dissolved in EtOAc (300 mL), quenched with sat. aqueous Na(HCO3)2 (200 mL). The organic layer was separated, washed with brine, dried over MgSO4 and concentrated to afford the compound, methyl-5-bromo-2-chloronicotinate, as a while solid (quantitative yield). LC-MS (M+H)=250.1.

Workup

  1. temperatureThe reaction was cooled to RT
  2. customthe volatile components removed in vacuo
  3. dissolutionThe crude residue was dissolved in EtOAc (300 mL)
  4. customquenched with sat. aqueous Na(HCO3)2 (200 mL)
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-b1946e536afc49dfbd37a19cd173e20b
Source dataset
uspto-grants-2014_10
Patent number
US08853237B2

Reaction notes

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