Water → 6-Chloro-4-o-tolyl-nicotinamide

HRID 1969168Notes

Reaction equation

HRID 1969168 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[CH3:17])[C:5]([C:6](O)=[O:7])=[CH:4][N:3]=1.S(Cl)(Cl)=O.[OH-].[NH4+:23].O>C1COCC1.CN(C=O)C>[Cl:1][C:2]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[CH3:17])[C:5]([C:6]([NH2:23])=[O:7])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 14923Ammonium HydroxideHCID 24386Thionyl ChlorideHCID 121673176-Chloro-4-o-tolyl-nicotinic acid

Product 1

HCID 121673186-Chloro-4-o-tolyl-nicotinamideYield 98%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 8.0 g (32.3 mMol) 6-chloro-4-o-tolyl-nicotinic acid in 48.0 ml THF were added 3.1 ml (42.0 mMol) thionylchloride and 143. mu.l (1.8 mMol) DMF. After 2 hours at 50° C., the reaction mixture was cooled to room temperature and added to a solution of 72.5 ml aqueous ammonium hydroxide 25% and 96 ml water cooled to 0° C. After 30 minutes at 0° C., THF was removed under reduced pressure and the aqueous layer was extracted with ethyl acetate. Removal of the solvent yielded 7.8 g (98%) 6-chloro-4-o-tolyl-nicotinamide as a beige crystalline foam. MS (ISP): 247 (M+H+, 100).

Workup

  1. temperaturecooled to 0° C
  2. waitAfter 30 minutes at 0° C.
  3. customTHF was removed under reduced pressure
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. customRemoval of the solvent

Sources & evidence

ORD record
ord-7ab9542a88e3446d88c1d521e9fd1e82
Source dataset
uspto-grants-2013_04
Patent number
US08426450B1

Reaction notes

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