Oxalyl chloride → {2-[2-(4-Chloro-phenyl)-3-cyclopentyl-propionylamino]-thiazol-4-yl}-acetic acid ethyl ester
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:12][CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)[C:9]([OH:11])=O)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[CH2:24]([O:26][C:27](=[O:35])[CH2:28][C:29]1[N:30]=[C:31]([NH2:34])[S:32][CH:33]=1)[CH3:25].C(N(CC)C(C)C)(C)C>C(Cl)Cl.CN(C)C=O>[CH2:24]([O:26][C:27](=[O:35])[CH2:28][C:29]1[N:30]=[C:31]([NH:34][C:9](=[O:11])[CH:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[CH2:12][CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)[S:32][CH:33]=1)[CH3:25]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 0 °C
Procedure
A solution of 2-(4-chloro-phenyl)-3-cyclopentyl-propionic acid (252 mg, 1.0 mmol) in methylene chloride (10 mL) was cooled to 0° C. and then treated with a 2.0 M solution of oxalyl chloride in methylene chloride (0.55 mL, 1.1 mmol) and a few drops of N,N-dimethylformamide. The reaction mixture was stirred at 0° C. for 15 min and then at 25° C. for 1.5 h. The reaction mixture was then treated with (2-amino-thiazol-4-yl)-acetic acid ethyl ester (409 mg, 2.2 mmol) and N,N-diisopropylethylamine (0.5 mL, 2.4 mmol). This solution was stirred at 25° C. for 24 h. At this time, the reaction was concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 85/15 hexanes/ethyl acetate) afforded {2-[2-(4-chloro-phenyl)-3-cyclopentyl-propionylamino]-thiazol-4-yl}-acetic acid ethyl ester (183.3 mg, 43.5%) as a pale yellow oil: EI-HRMS m/e calcd for C21H25ClN2O3S (M+) 420.1274, found 420.1272.
Workup
- waitat 25° C. for 1.5 h
- stirringThis solution was stirred at 25° C. for 24 h
- concentrationAt this time, the reaction was concentrated in vacuo
Sources & evidence
- ORD record
- ord-4a2d56b1249440eaa4ab2767c73941e9
- Source dataset
- uspto-grants-2001_11
- Patent number
- US06320050B1
Reaction notes
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