Triethylamine → 4-Bromo-N-methoxy-N-methylpicolinamide

HRID 1038653Notes

Reaction equation

HRID 1038653 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([OH:10])=O)[CH:3]=1.C([N:13]([CH2:16]C)CC)C.[C:18](C1NC=CN=1)(C1NC=CN=1)=[O:19]>C1COCC1>[CH3:18][O:19][N:13]([CH3:16])[C:8]([C:4]1[CH:3]=[C:2]([Br:1])[CH:7]=[CH:6][N:5]=1)=[O:10]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 7351504-Bromopyridine-2-carboxylic acidHCID 5250894Bis-(1H-imidazol-2-YL)-methanone

Product 1

HCID 581917694-Bromo-N-methoxy-N-methylpicolinamideYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of commercially-available 4-bromopicolinic acid (10.0 g, 49.5 mmole) in 200 mL of anhydrous THF at room temperature is added N,O-hydroxylamine hydrochloride (4.83 g, 49.5 mmol), triethylamine (6.9 mL, 49.5 mmol), carbonyl diimidazole (CDl) (12.0 g, 74.3 mmol) and N,N-dimethyl amino pyridine (DMAP) (20 mg, 0.16 mmol). After stirring at room temperature for 4 hours, an aliquot is taken and injected on LC-MS to check the reaction progress. Upon completion of the reaction, the reaction mixture is quenched with 100 mL of water and extracted with 2×150 mL of ethyl acetate. The combined organic layers are concentrated and purified by chromatography (hexanes 95%, EtOAc 5% step gradient) to give 4-bromo-pyridine-2-carboxylic acid methoxy-methyl-amide (1) as a thick yellow oil (10.4 g, yield 86%) MS ES+247.02.

Workup

  1. customUpon completion of the reaction
  2. customthe reaction mixture is quenched with 100 mL of water
  3. extractionextracted with 2×150 mL of ethyl acetate
  4. concentrationThe combined organic layers are concentrated
  5. custompurified by chromatography (hexanes 95%, EtOAc 5% step gradient)

Sources & evidence

ORD record
ord-986b75ea6f2e453389233e3e68f03f3f
Source dataset
uspto-grants-2013_10
Patent number
US08552003B2

Reaction notes

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