反应详情

To a solution of (3S,4R)-3-hydroxymethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (200 mg, 0.404 mmol) in ether (12 mL) are successively added (S)-1-phenylpropyl isocyanate (130.4 mg, 0.809 mmol) and AlCl3 (54 mg, 0.404 mmol). The mixture is stirred at RT under nitrogen overnight. (S)-1-phenylpropyl isocyanate (150 μL) and AlCl3 (54 mg, 0.404 mmol) are again added and the mixture further stirred for 5 h. AcOEt is added and the reaction mixture quenched by the addition of an aqueous saturated solution of NaHCO3. The layers are separated and the aqueous one back extracted twice with AcOEt. The combined organic extracts are dried over Na2SO4, filtered and concentrated under reduced pressure. The crude mixture is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 100:0 to 95:5) to give the title product TLC, Rf (CH2Cl2/MeOH 95:5)=0.35. MS (LC-MS): 656.2 [M+H]+; tR (HPLC, Nucleosil C18-HD column, 20-100% CH3CN/H2O/6 min, 100% CH3CN/1.5 min, flow: 1 ml/min): 3.94 min.

1. stirringthe mixture further stirred for 5 h
2. customthe reaction mixture quenched by the addition of an aqueous saturated solution of NaHCO3
3. customThe layers are separated
4. extractionthe aqueous one back extracted twice with AcOEt
5. dry with materialThe combined organic extracts are dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe crude mixture is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 100:0 to 95:5)