Acetic Acid → Methyl 2-chloro-6-methylpyridine-3-carboxylate

HRID 1873995Notes

Reaction equation

HRID 1873995 reaction equation
[CH3:1]COCC.C[Si](C=[N+]=[N-])(C)C.[Cl:13][C:14]1[N:22]=[C:21]([CH3:23])[CH:20]=[CH:19][C:15]=1[C:16]([OH:18])=[O:17].CC(O)=O>C1COCC1.CO>[Cl:13][C:14]1[N:22]=[C:21]([CH3:23])[CH:20]=[CH:19][C:15]=1[C:16]([O:18][CH3:1])=[O:17]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 3283Diethyl EtherHCID 1217242-Chloro-6-methylnicotinic acidHCID 167693Trimethylsilyldiazomethane

Product 1

HCID 13055804Methyl 2-chloro-6-methylpyridine-3-carboxylateYield 93%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A 2 M ether solution of (trimethylsilyl)diazomethane (30 mL, 60.0 mmol) was added to a solution of 2-chloro-6-methylnicotinic acid (8 g, 45.2 mmol) in THF (100 mL) and MeOH (25 mL) in a room temperature water bath. After 30 min, HOAc (2 mL) was added. The mixture was concentrated and purified by silica gel chromatography, eluting with 0-20% EtOAc in hexanes, to give methyl 2-chloro-6-methylnicotinate as colorless oil (7.77 g, 93% yield). MS (ES+) m/z: 186 (M+H); LC retention time: 2.64 min (analytical HPLC Method A).

Workup

  1. concentrationThe mixture was concentrated
  2. custompurified by silica gel chromatography
  3. washeluting with 0-20% EtOAc in hexanes

Sources & evidence

ORD record
ord-c717c5ab590447328944b8d0653959a2
Source dataset
uspto-grants-2012_11
Patent number
US08304539B2

Reaction notes

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