Triethylamine → (Z)-Ethyl 3-(dimethylamino)-2-(3-fluoropicolinoyl)acrylate

HRID 1497690

Reaction equation

HRID 1497690 reaction equation
[CH3:1][N:2]([CH3:10])/[CH:3]=[CH:4]/[C:5]([O:7][CH2:8][CH3:9])=[O:6].C(N(CC)CC)C.[F:18][C:19]1[C:20]([C:25](Cl)=[O:26])=[N:21][CH:22]=[CH:23][CH:24]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:1][N:2]([CH3:10])/[CH:3]=[C:4](/[C:25](=[O:26])[C:20]1[C:19]([F:18])=[CH:24][CH:23]=[CH:22][N:21]=1)\[C:5]([O:7][CH2:8][CH3:9])=[O:6]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 5369162Ethyl trans-3-dimethylaminoacrylateHCID 861023073-Fluoropyridine-2-carbonyl chloride

Product 1

HCID 86725445(Z)-Ethyl 3-(dimethylamino)-2-(3-fluoropicolinoyl)acrylateYield 16.6%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
83 °C

Procedure

To a light yellow solution of (E)-ethyl 3-(dimethylamino)acrylate (5.15 g, 36.0 mmol) in toluene (50 mL) was added triethylamine (3.64 g, 5.02 mL, 36.0 mmol) at room temperature. To this, a dark brown suspension of 3-fluoropicolinoyl chloride (30) (4.79 g, 30 mmol) in toluene (50 mL, heated to dissolve, but not dissolved completely) was added in one portion using a funnel. Then, the resulting dark brown solution was heated to 83° C. and stirred for 1.5 h at this temperature. During this period, it turned to a dark brown solution and TLC analysis indicated the presence of a new spot. Then, the heating was stopped and the dark brown mixture was diluted with ethyl acetate (200 mL) and the brown solution was washed with water, brine solution, and dried over anhydrous MgSO4. Filtration and concentration gave the crude brown mixture which was purified using ISCO (120 g) column chromatography, eluting with ethyl acetate in hexanes (0 to 100%) and then 5 to 20% methanol in dichloromethane. The desired fractions were combined and the solvent was removed under vacuum to obtain the (Z)-ethyl 3-(dimethylamino)-2-(3-fluoropicolinoyl)acrylate (31) (1.33 g, 15% yield) as a dark brown paste.

Workup

  1. temperatureheated
  2. dissolutionto dissolve
  3. dissolutionnot dissolved completely)
  4. additionwas added in one portion
  5. waitDuring this period
  6. washthe brown solution was washed with water, brine solution
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationFiltration and concentration
  9. customgave the crude brown mixture which
  10. customwas purified
  11. washeluting with ethyl acetate in hexanes (0 to 100%)
  12. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-cf5c752ae14e40ab8d18cc68d78a5194
Source dataset
uspto-grants-2015_12
Patent number
US09199987B2

Linked notes

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