1-Amino-2-propanol → N1-(2-hydroxypropyl)-N2-(3-(trifluoromethyl)phenyl)oxalamide

HRID 1259313Notes

Reaction equation

HRID 1259313 reaction equation
[O:1]=[C:2]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=1)[C:3]([O:5]CC)=O.[NH2:19][CH2:20][CH:21]([OH:23])[CH3:22]>C(O)C>[OH:23][CH:21]([CH3:22])[CH2:20][NH:19][C:3](=[O:5])[C:2]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:16])([F:17])[F:18])[CH:10]=1)=[O:1]

Participants

4

Reactant 2

HCID 41-Amino-2-propanolHCID 1805242ethyl 2-oxo-2-[3-(trifluoromethyl)anilino]acetate

Product 1

HCID 2917089N1-(2-hydroxypropyl)-N2-(3-(trifluoromethyl)phenyl)oxalamideYield 84.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
22.5 °C

Procedure

Ethanol (1.27 L) and ethyl oxo{[3-(trifluoromethyl)phenyl]amino}acetate (243.15 g, 1 eq) were heated to reflux. 1-Amino-2-propanol (73.2 g, 1.05 eq) in ethanol (0.29 L) was added to the reaction mixture over 1 hour. The reaction mixture was held at reflux for a further 3 hours and then cooled to 20-25° C. The solvent was removed on a rotary evaporator and the resulting white solid was dissolved in ethyl acetate (1.6 L). The solution was reduced in volume by 80% by distillation at atmospheric pressure. Heptane (1.29 L) was then added and the product precipitated. The mixture was cooled further to 0-5° C. and held at this temperature for 1 hour. The mixture was filtered and the filter cake washed with heptane (0.24 L). The damp product was dried at 50° C. for 16 hours in a vacuum oven. The title compound (227.88 g, 84.3%) was isolated as a white crystalline solid.

Workup

  1. temperatureat reflux for a further 3 hours
  2. customThe solvent was removed on a rotary evaporator
  3. dissolutionthe resulting white solid was dissolved in ethyl acetate (1.6 L)
  4. distillationThe solution was reduced in volume by 80% by distillation at atmospheric pressure
  5. additionHeptane (1.29 L) was then added
  6. customthe product precipitated
  7. temperatureThe mixture was cooled further to 0-5° C.
  8. filtrationThe mixture was filtered
  9. washthe filter cake washed with heptane (0.24 L)
  10. customThe damp product was dried at 50° C. for 16 hours in a vacuum oven

Sources & evidence

ORD record
ord-700b0d1fe92440bd84275d1e37e6eaf8
Source dataset
uspto-grants-2013_06
Patent number
US08466284B2

Reaction notes

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