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

HRID 521325Notes

Reaction equation

HRID 521325 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. Half of the reaction mixture was added to separate flasks and deionized water (3 L) was added to each flask and were 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. additionHalf of the reaction mixture was added
  3. customto separate flasks
  4. additiondeionized water (3 L) was added to each flask
  5. stirringwere stirred for 1 hour
  6. filtrationThe resulting precipitate in each flask was harvested by filtration
  7. customdried under reduced pressure
  8. customThe crude product was recrystallized from ethyl acetate
  9. filtrationfiltered

Sources & evidence

ORD record
ord-0dbadc3d39c6417da083a172ee92a1c0
Source dataset
uspto-grants-2016_05
Patent number
US09328110B2

Reaction notes

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