N-bromobutanimide → Ethyl 6-(bromomethyl)picolinate

HRID 2112995

Reaction equation

HRID 2112995 reaction equation
[Br:1]N1C(=O)CCC1=O.[CH2:9]([O:11][C:12]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[N:15]=1)=[O:13])[CH3:10]>C(Cl)(Cl)(Cl)Cl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[CH2:9]([O:11][C:12]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][Br:1])[N:15]=1)=[O:13])[CH3:10]

Participants

5

Reactant 2

HCID 67184N-bromobutanimide2×HCID 564597Ethyl 6-methylpyridine-2-carboxylate

Product 1

HCID 23033755Ethyl 6-(bromomethyl)picolinateYield 32.2%

Reagents, catalysts & solvents 2

HCID 7187Benzoyl PeroxideCatalyst2×HCID 5943Carbon TetrachlorideSolvent

Procedure

Finely ground N-bromo-succinimide (29.4 g, 165.2 mmol) was added in several portions to a solution of 6-methyl-pyridine-2-carboxylic acid ethyl ester (24.7 g, 150.0 mmol; available from Aldrich Chemical Company, Inc., Milwaukee, Wis.) in carbon tetrachloride (500 mL), and then benzoyl peroxide (100 mg, 0.4 mmol) was added. The mixture was heated at 84 degrees under nitrogen for approximately 40 h. Further portions of N-bromo-succinimide (14.8 g, 83.2 mmol) and then benzoyl peroxide (100 mg, 0.4 mmol) were added and heating was continued overnight. The reaction mixture was cooled to room temperature, filtered, evaporated, and purified by chromatography on silica gel using a Biotage system, eluting with 1:1 dichloromethane/hexane and dichloromethane to give 6-bromomethyl-pyridine-2-carboxylic acid ethyl ester (11.8 g, 32%) as a pale yellow oil. MS (MH+): 244/246. From HPLC, the purity was estimated at 85-90% and the material was used in the next step without further purification.

Workup

  1. temperatureThe mixture was heated at 84 degrees under nitrogen for approximately 40 h
  2. temperatureheating
  3. filtrationfiltered
  4. customevaporated
  5. custompurified by chromatography on silica gel using a Biotage system
  6. washeluting with 1:1 dichloromethane/hexane and dichloromethane

Sources & evidence

ORD record
ord-782978d24abb48a3b96654c63a9d5596
Source dataset
uspto-grants-2009_04
Patent number
US07524870B2

Linked notes

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