反应详情

温度

20 °C

To a solution of 1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carboxylic acid, Intermediate 119 (1 eq.) in DCM under nitrogen, was added DMF (0.01 eq.) then oxalyl chloride (2 eq.). The solution was stirred at 20° C. for 30 min, then cooled to 0° C. A solution of (4-Chloro-benzylamino)-acetic acid methyl ester (1.5 eq.) and either TEA or DIPEA (2 to 7 eq.) in DCM was then added to the previous mixture. The solution was stirred at 0° C. for 1 h then at 20° C. until completion (1 h). The reaction was quenched with a saturated aqueous solution of NaHCO3 and extracted three times with DCM. The organic layers were combined, dried over MgSO4, filtered and concentrated under reduced pressure. The crude was purified by chromatography on silica gel (elution with heptane/EtOAc: 1/0 to 1/1) to afford ((4-chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-acetic acid methyl ester.

1. temperaturecooled to 0° C
2. stirringThe solution was stirred at 0° C. for 1 h
3. customat 20° C.
4. customuntil completion (1 h)
5. customThe reaction was quenched with a saturated aqueous solution of NaHCO3
6. extractionextracted three times with DCM
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe crude was purified by chromatography on silica gel (elution with heptane/EtOAc: 1/0 to 1/1)