Tert-Butylamine → N-tert-butyl-6-chloronicotinamide

HRID 379423Notes

Reaction equation

HRID 379423 reaction equation
S(Cl)(Cl)=O.[Cl:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([OH:12])=O)=[CH:8][N:7]=1.[C:15]([NH2:19])([CH3:18])([CH3:17])[CH3:16].[OH-].[Na+]>C1(C)C=CC=CC=1.CN(C=O)C>[C:15]([NH:19][C:10](=[O:12])[C:9]1[CH:13]=[CH:14][C:6]([Cl:5])=[N:7][CH:8]=1)([CH3:18])([CH3:17])[CH3:16]

Participants

7

Reactant 4

HCID 6385Tert-ButylamineHCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 792226-Chloronicotinic acid

Product 1

HCID 11816697N-tert-butyl-6-chloronicotinamideYield 94%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

25.7 ml (349 mMol) Thionylchloride and 0.5 ml (6.35 mMol) DMF were added to a suspension of 50.0 g (317 mMol) 6-chloro-nicotinic acid in 250 ml toluene and the reaction mixture was heated to 80° C. for 2 hours. After cooling to 10° C., 100.5 ml (952 mMol) tert.-butylamine were added over 40 minutes and stirring was pursued for 30 minutes at the same temperature. 250 ml Aqueous sodium hydroxide 2N were added and the mixture was stirred 30 minutes at room temperature. Dilution with 300 ml water and extraction with ethyl acetate yielded 63.3 g (94%) N-tert.-butyl-6-chloro-nicotinamide as a beige powder of m.p. =108-110° C.

Workup

  1. temperatureAfter cooling to 10° C.
  2. stirringthe mixture was stirred 30 minutes at room temperature
  3. extractionDilution with 300 ml water and extraction with ethyl acetate

Sources & evidence

ORD record
ord-aa3fc31279f84d88b397d8cc83d8e219
Source dataset
uspto-grants-2001_10
Patent number
US06297375B1

Reaction notes

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