Diisopropylamine → 1,1-Dimethylethyl 1-oxo-3-(4-chlorophenyl)-2-cyclopropyl-2,7-diazaspiro[3.5]nonane-7-carboxylate

関与物質

反応手順

Cool to 0 to −10 C, a solution of diisopropylamine (6.0 mL) in THF (10 mL) and add n-butyllithium (2.5 M, 16.6 mL) dropwise. After 1 h, the reaction mixture was cooled to −78 C. Add a solution of ethyl 1-tert-butoxycarbonylpiperidine-4-carboxylate (1) (10 g) in anhydrous THF (20 mL) dropwise, and stir the resulting solution at −78 C for 1.5 h. Add 4-chlorobenzylidene cyclopropylamine (8) (6.69 g) in THF (40 mL) and stir for 1 h. Warm the reaction mixture to room temperature and stir overnight. Quench the reaction mixture with saturated ammonium chloride solution and extract with EtOAc. Partition the EtOAc solution with IN HCl, then salt solution. Concentrate the dried (MgSO4) EtOAc solution in vacuo to give an amber oil (13.83 g). Absorb the amber oil (12.8 g) on Purasil 60A 230-400 mesh (˜30 mL), place in a syringe cartridge, and elute onto a Redi Sep Normal Phase Disposable Column (330 g, ISCO). Elute with hexane (one column volume) then hexane/EtOAc gradient (0% to 55% EtOAc) at 65 mL/min. Collect the title compound and concentrate the fractions in vacuo to give the title compound (9) (3.49 g).

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