Reaction equation
[CH2:1]([O:3][C:4]([CH2:6][NH:7][C:8]([C:10]([NH:12][CH2:13][C:14](=O)[CH3:15])=[O:11])=[O:9])=[O:5])[CH3:2].FC(F)(F)C(O)=O.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(O)(=O)C>[CH2:1]([O:3][C:4]([CH2:6][N:7]1[C:14]([CH3:15])=[CH:13][N:12]=[C:10]([OH:11])[C:8]1=[O:9])=[O:5])[CH3:2]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
To a stirred solution of N-(ethoxycarbonylmethyl)-N′-(2-oxo-1-propyl) oxamide (6.9 g, 30 mmol), as prepared in the preceding step, trifluoroacetic acid (2.32 mL, 30 mmol) and trifluoroacetic anhydride (4.3 mL, 30 mmol) in acetic acid (100 mL) was heated to 80° C. under nitrogen for 10 hours. Additional trifluoroacetic acid (1.5 mL, 20 mmol) and trifluoroacetic anhydride (3.0 mL, 20 mmol) were added, the mixture was stirred at 80° C. for additional 24 hours under nitrogen. After cooling to room temperature, the solvent was removed under reduced pressure. The residue was stirred with acetic acid (13 mL) for 15 minutes at 60° C., then ethyl acetate and hexane (4:1, 60 mL) were added dropwise to the warm mixture. The precipitates were allowed to cool to room temperature, filtered, and dried under high vacuum to give the title compound as an off-white solid (4.9 g, 77%). 1H NMR (400 MHz, CDCl3) δ 11.20 (s(br), 1H), 6.17 (s, 1H), 4.66 (s, 2H), 4.24 (q, 2H, J=7.1 Hz), 2.27 (s, 3H), 1.30 (t, 3H, J=7.1 Hz).
Workup
- temperatureAfter cooling to room temperature
- customthe solvent was removed under reduced pressure
- stirringThe residue was stirred with acetic acid (13 mL) for 15 minutes at 60° C.
- additionethyl acetate and hexane (4:1, 60 mL) were added dropwise to the warm mixture
- temperatureto cool to room temperature
- filtrationfiltered
- customdried under high vacuum
Sources & evidence
- ORD record
- ord-30c3ee271b9f4317ae64965d159c3d5f
- Source dataset
- uspto-grants-2002_11
- Patent number
- US06476016B2
Linked notes
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