反应详情

To a solution of (3S,4R)-3-formyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (2.7 g, 5.48 mmol) in MeOH (containing 2% AcOH, 25 mL), methylamine (13.7 mL, 27.41 mmol, 2M in MeOH) is added. The solution is stirred at RT for 1 h under nitrogen atmosphere and cooled to 10° C., before the careful addition of NaBH4 (0.415 g, 10.96 mmol) (exothermic !!). The resulting mixture is allowed to reach RT and stirred for 1.5 h. The excess reducing agent is quenched with water, AcOEt is added and the reaction mixture is poured into an aqueous saturated solution of NaHCO3. The organic layer is separated and the aqueous layer extracted twice with AcOEt, dried over Na2SO4, filtered, and concentrated in vacuo. The crude material is used in the next step without further purification. TLC, Rf (CH2Cl2/MeOH 95:5)=0.05. MS (LC-MS) [M+H]+=508.1. tR (HPLC, Macherey-Nagel 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): 4.53 min.

1. customto reach RT
2. stirringstirred for 1.5 h
3. customis quenched with water, AcOEt
4. additionis added
5. additionthe reaction mixture is poured into an aqueous saturated solution of NaHCO3
6. customThe organic layer is separated
7. extractionthe aqueous layer extracted twice with AcOEt
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe crude material is used in the next step without further purification
12. customtR (HPLC, Macherey-Nagel 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)
13. custom4.53 min.