Reaction #1605776

Reaction equation

2-(5-methylpyridin-2-yl)ethanamine

(2-methoxy-4-methylphenyl)methanamine

Et3N

ethyl 2-chloro-2-oxoacetate

→

N1-(2-methoxy-4-methylbenzyl)-N2-(2-(5-methylpyridin-2-yl)ethyl)oxalamide

Yield 15.0%

Solvents

CH3CN

Conditions

Workup

1. 1
   workup.ADDITIONAfter the addition
2. 2
   TemperatureThe reaction was heated
3. 3
   Temperatureat reflux for 24 hours
4. 4
   TemperatureAfter cooling the solvent
5. 5
   Otherwas removed under reduced pressure
6. 6
   workup.DISSOLUTIONthe residue was dissolved in ethyl acetate
7. 7
   Washwashed successively with water and brine
8. 8
   Dryingdried over MgSO4
9. 9
   Filtrationfiltered
10. 10
    Otherevaporated
11. 11
    OtherThe residue was chromatographed on silica gel (eluent: 25-35% acetone in hexane)
12. 12
    Otherrecrystallized from ethyl acetate/hexane and ethanol/water

Procedure

A mixture of 2 g of (2-methoxy-4-methylphenyl)methanamine (from step 3) and Et3N (3.7 mL, 2 eq) in dry CH3CN (45 mL) was cooled to 0° C. under N2 atmosphere and ethyl 2-chloro-2-oxoacetate (1.47 mL, 1 eq) was added dropwise. After the addition was complete, the reaction mixture was stirred at room temperature for 4 hours and 2-(5-methylpyridin-2-yl)ethanamine (2.52 g, 1.4 eq, from step 5) was added. The reaction was heated at reflux for 24 hours. After cooling the solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate and washed successively with water and brine, dried over MgSO4, filtered and evaporated. The residue was chromatographed on silica gel (eluent: 25-35% acetone in hexane) and recrystallized from ethyl acetate/hexane and ethanol/water to give 650 mg of N1-(2-methoxy-4-methylbenzyl)-N2-(2-(5-methylpyridin-2-yl)ethyl)oxalamide (15%).

Source