Methyl iodide → Methyl 6-chloro-5-methoxynicotinate

HRID 1924851Notes

Reaction equation

HRID 1924851 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8]([OH:10])[C:7]([Cl:11])=[N:6][CH:5]=1.CI.[C:15](=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8]([O:10][CH3:15])[C:7]([Cl:11])=[N:6][CH:5]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 46941479Methyl 6-chloro-5-hydroxynicotinate

Product 1

HCID 57336616Methyl 6-chloro-5-methoxynicotinateYield 68.7%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of 6-chloro-5-hydroxynicotinic acid methyl ester (1.8 g, 9.6 mmol), methyl iodide (2 M solution in Et2O, 5.8 mL, 11.6 mmol) and potassium carbonate (2.0 g, 14.5 mmol) in acetone (190 mL) was refluxed for 6 h. The reaction was then concentrated via rotavap and H2O was added (100 mL). The resulting white precipitate was filtered and rinsed with additional H2O to furnish the product 6-chloro-5-methoxynicotinic acid methyl ester as a white solid (1.33 g, 68%); mp=83-85° C.; 1H NMR (400 MHz, CDCl3) δ 8.60 (d, 1H), 7.77 (d, 1H), 3.98 (s, 3H), 3.96 (s, 3H): GC-MS: Exact mass calcd for C8H8ClNO3 [M]+, 201. Found 201.

Workup

  1. temperaturewas refluxed for 6 h
  2. concentrationThe reaction was then concentrated via rotavap
  3. additionH2O was added (100 mL)
  4. filtrationThe resulting white precipitate was filtered
  5. washrinsed with additional H2O

Sources & evidence

ORD record
ord-70a46ac6d8d843dbbc152a0f1d484c1b
Source dataset
uspto-grants-2012_05
Patent number
US08178565B2

Reaction notes

Loading…