Triethylamine → Ethyl 4-[(2-chloro-5,6-dimethyl-3-nitropyridin-4-yl)amino]butyrate

HRID 1623106Notes

Reaction equation

HRID 1623106 reaction equation
[Cl:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6](Cl)[C:5]([CH3:12])=[C:4]([CH3:13])[N:3]=1.Cl.[NH2:15][CH2:16][CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20].C(N(CC)CC)C>CN(C)C=O>[Cl:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([NH:15][CH2:16][CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:5]([CH3:12])=[C:4]([CH3:13])[N:3]=1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 121091232,4-Dichloro-5,6-dimethyl-3-nitropyridineHCID 126496614-Aminobutyrate ethyl hydrochloride2×

Product 1

HCID 57455392Ethyl 4-[(2-chloro-5,6-dimethyl-3-nitropyridin-4-yl)amino]butyrateYield 55.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2,4-Dichloro-5,6-dimethyl-3-nitropyridine (135.0 g, 0.488 mol) and ethyl 4-aminobutyrate hydrochloride (114.0 g, 0.683 mol) were triturated in N,N-dimethylformamide (675 mL) (DMF) at 0° C. Triethylamine (272.6 mL, 1.95 mol) was added to generate a brown slurry. After 15 minutes, the reaction mixture was allowed to warm to ambient temperature and the reaction was stirred overnight. Analysis by 1H NMR indicated the reaction was incomplete. An additional amount of triethylamine (102.2 mL, 0.73 mol) and ethyl 4-aminobutyrate hydrochloride (35.28 g, 0.159 mol) in DMF (200 mL) were added to the reaction mixture and allowed to stir over an additional 24 hours. The incomplete reaction mixture was separated into 2 equal sized aliquots. Each aliquot was combined with water (3 L) and stirred for 1 hour. The resulting precipitate in each flask was harvested by filtration and dried under reduced pressure. The crude product was recrystallized from ethyl acetate and filtered to yield 86.20 g of ethyl 4-[(2-chloro-5,6-dimethyl-3-nitropyridin-4-yl)amino]butyrate as a yellow granular solid.

Workup

  1. stirringto stir over an additional 24 hours
  2. customThe incomplete reaction mixture was separated into 2
  3. stirringstirred for 1 hour
  4. filtrationThe resulting precipitate in each flask was harvested by filtration
  5. customdried under reduced pressure
  6. customThe crude product was recrystallized from ethyl acetate
  7. filtrationfiltered

Sources & evidence

ORD record
ord-7eb420aaad3041aab6503d93f3d9cac2
Source dataset
uspto-grants-2014_07
Patent number
US08778963B2

Reaction notes

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