反应详情

To a solution of (3R*,4R*)-3-[(cyclopropanecarbonyl-methyl-amino)-methyl]-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (154 mg, 0.267 mmol) in 3 mL CH2Cl2, TFA (309 μL, 4.01 mmol) is added. The mixture is stirred 4 h at RT, and poured into a saturated solution of NaHCO3. The layers are separated, and the aqueous one is back-extracted twice with CH2Cl2. The combined organic extracts are dried over Na2SO4, filtered and concentrated. The crude material is purified by flash chromatography on Isolute SPE Flash NH2 column (eluent: CH2Cl2/MeOH 100:0 to 95:5) to give the title product. TLC, Rf (SiO2—NH2, CH2Cl2/MeOH 95:5)=0.1. MS (LC-MS): 476.1 [M+H]+; tR (HPLC, Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mL/min): 4.10 min.

1. customThe layers are separated
2. extractionthe aqueous one is back-extracted twice with CH2Cl2
3. dry with materialThe combined organic extracts are dried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe crude material is purified by flash chromatography on Isolute SPE Flash NH2 column (eluent: CH2Cl2/MeOH 100:0 to 95:5)