Azobisisobutyronitrile → 2-Chloro-5-(chloromethyl)-3-fluoropyridine

HRID 552919

Reaction equation

HRID 552919 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[F:9].[Cl:10]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N>ClC1C=CC=CC=1>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][Cl:10])=[CH:4][C:3]=1[F:9]

Participants

5

Reactant 3

HCID 6547Azobisisobutyronitrile2×HCID 31398Chlorosuccinimide2×HCID 135413652-Chloro-3-fluoro-5-methylpyridine

Product 1

HCID 216982012-Chloro-5-(chloromethyl)-3-fluoropyridineYield 53%

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent

Procedure

1.00 g (6.87 mmol) of 6-chloro-5-fluoro-3-methylpyridine (F. L. Setliff, Organic Preparations and Procedures International 1971, 3, 217-222), 1.01 g (7.56 mmol) of N-chlorosuccinimide and 0.11 g (0.69 mmol) of 2,2′-azobis(2-methylpropionitrile) in 100 ml of chlorobenzene are boiled under reflux for 2 days. After about 16 hours and 32 hours, in each case a further 1.01 g (7.56 mmol) of N-chlorosuccinimide and 0.11 g (0.69 mmol) of 2,2′-azobis(2-methylpropionitrile) are added. The reaction mixture is washed with saturated aqueous sodium sulphite solution and sodium bicarbonate solution and then dried over sodium sulphate and concentrated under reduced pressure. Column chromatography of the residue on silica gel (silica gel 60—Merck, particle size: 0.04 to 0.063 mm) using the mobile phase mixture ethyl acetate:cyclohexane (1:20) gives 0.65 g (53% of theory) of 6-chloro-3-chloromethyl-5-fluoropyridine.

Workup

  1. temperatureunder reflux for 2 days
  2. washThe reaction mixture is washed with saturated aqueous sodium sulphite solution and sodium bicarbonate solution
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d0c373abcb374ea0950a9a5dd295a3ec
Source dataset
uspto-grants-2011_05
Patent number
US07951951B2

Linked notes

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