Methyl iodide → Methyl 3-chloroisonicotinate

HRID 1873991

Reaction equation

HRID 1873991 reaction equation
[C:1](=O)([O-])[O-].[K+].[K+].[Cl:7][C:8]1[CH:16]=[N:15][CH:14]=[CH:13][C:9]=1[C:10]([OH:12])=[O:11].CI>CS(C)=O>[Cl:7][C:8]1[CH:16]=[N:15][CH:14]=[CH:13][C:9]=1[C:10]([O:12][CH3:1])=[O:11]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 27358163-Chloropyridine-4-carboxylic acid

Product 1

HCID 15324397Methyl 3-chloroisonicotinateYield 56%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

Potassium carbonate (36.3 g, 263 mmol) was added to 3-chloroisonicotinic acid (10.35 g, 65.7 mmol) in DMSO (50 mL). After 30 min, MeI (8.22 mL, 131 mmol) was added. The mixture was stirred at room temperature for 2 h, quenched with saturated NH4Cl (300 mL) and water (200 mL), and extracted with EtOAc (3×200 mL). The combined extracts were washed with brine (2×50 mL), dried (MgSO4) and concentrated. Silica gel chromatography, eluting with 10-30% ethyl acetate in hexanes, gave methyl 3-chloroisonicotinate as a colorless liquid (6.275 g, 56% yield). MS (ES+) m/z: 172 (M+H); LC retention time: 2.45 min (analytical HPLC Method A).

Workup

  1. customquenched with saturated NH4Cl (300 mL) and water (200 mL)
  2. extractionextracted with EtOAc (3×200 mL)
  3. washThe combined extracts were washed with brine (2×50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. washSilica gel chromatography, eluting with 10-30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-9804765ee1dc41b4b56017fcd5343ca9
Source dataset
uspto-grants-2012_11
Patent number
US08304539B2

Linked notes

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