反应详情

To a stirred solution of (R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)propionyl]-3-piperidine carboxylic acid (1.0 g) and N,N-dimethylformamide (210 μl) in dichloromethane (10 ml) was added dropwise oxalyl chloride (240 μl) at 4° C. under a nitrogen atmosphere. To an ice cooled solution of 2(S)-benzyloxycarbonylamino-β-alanine methyl ester hydrochloride (940 mg) and N-(trimethylsilyl)-acetamide (2.85 g) in N,N-dimethylformamide (10 ml) was added dropwise the above solution with stirring under a nitrogen atmosphere. The reaction mixture was allowed to warm to ambient temperature, and stirred for 2 hours, which was partitioned between a mixture of ethyl-acetate and n-hexane and water. The organic layer was separated, washed in turn with water, aqueous 5% NaHCO3 solution and brine, and dried over MgSO4. Evaporation of the solvent gave a residue, which was purified by silica-gel column chromatography eluting with n-hexane-ethyl acetate (from 1:6 to ethyl acetate only) to give N-[(R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)propionyl]-3-piperidylcarbonyl]-2(S)-benzyloxycarbonylamino-β-alanine methyl ester (0.89 g) as a foam, which is the same compound obtained in Preparation 15.

1. stirringstirred for 2 hours
2. customwhich was partitioned between a mixture of ethyl-acetate and n-hexane and water
3. customThe organic layer was separated
4. washwashed in turn with water, aqueous 5% NaHCO3 solution and brine
5. dry with materialdried over MgSO4
6. customEvaporation of the solvent
7. customgave a residue, which
8. customwas purified by silica-gel column chromatography
9. washeluting with n-hexane-ethyl acetate (from 1:6 to ethyl acetate only)