Diethylamine → 6-Chloro-N,N-diethylnicotinamide

HRID 1017494Notes

Reaction equation

HRID 1017494 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.[CH2:15]([NH:17][CH2:18][CH3:19])[CH3:16].[OH-].[Na+]>O1CCCC1.C(OCC)(=O)C.O.CN(C=O)C>[Cl:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([N:17]([CH2:18][CH3:19])[CH2:15][CH3:16])=[O:12])=[CH:8][N:7]=1

Participants

9

Reactant 4

HCID 8021DiethylamineHCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 792226-Chloronicotinic acid

Product 1

HCID 5878136-Chloro-N,N-diethylnicotinamideYield 50.4%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

0.51 ml (6.98 mMol) Thionylchloride and 10 μl DMF were added to a suspension of 1.0 g (6.34 mMol) 6-chloronicotinic acid in 5 ml tetrahydrofuran. The reaction mixture was stirred at 65° C. for 1.5 hours, cooled to 0° C. and 1.98 ml (19.0 mMol) diethylamine were added over 40 minutes. The resulting suspension was stirred 4 hours at room temperature and 1 hour at 60° C. After cooling to room temperature, 5.0 ml aqueous NaOH 2N were added and stirring pursued for 30 minutes. The system was diluted with 25 ml deionized water and 20 ml ethyl acetate. The phases were separated and the aqueous phase was further extracted with ethyl acetate. The combined organic extracts were washed with aqueous NaOH 1N and half-saturated aqueous NaCl, dried (Na2SO4) and evaporated to yield 0.68 g (50%) 6-chloro-N,N-diethyl-nicotinamide as a yellow oil.

Workup

  1. temperaturecooled to 0° C.
  2. stirringThe resulting suspension was stirred 4 hours at room temperature and 1 hour at 60° C
  3. temperatureAfter cooling to room temperature
  4. stirringstirring
  5. waitpursued for 30 minutes
  6. additionThe system was diluted with 25 ml
  7. customThe phases were separated
  8. extractionthe aqueous phase was further extracted with ethyl acetate
  9. washThe combined organic extracts were washed with aqueous NaOH 1N and half-saturated aqueous NaCl
  10. dry with materialdried (Na2SO4)
  11. customevaporated

Sources & evidence

ORD record
ord-49d83ac4a9ba45d7a62fa4fb842acff3
Source dataset
uspto-grants-2002_11
Patent number
US06479483B2

Reaction notes

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