1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 67377609, compound

Participants

Reaction Steps

N-Boc-4-(4-carboxyphenyl)piperidine (200 mg, 0.66 mmol) and 3-iodo-4-methyl aniline (153 mg, 0.72 mmol) in DCM (10 mL) was treated with EDCI (380 mg, 1.98 mmol) at rt. After stirring for 48 hr at rt the reaction mixture was partitioned between EtOAc and water. The EtOAc layer was collected, concentrated and the residue was chromatographed on a silica gel column with a 0-30% EtOAc in hexanes to afford the corresponding intermediate 4-[4-(3-Iodo-4-methyl-phenylcarbamoyl)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester. This intermediate was then dissolved in a 30% TFA in CH2Cl2 mixture (10 mL). Upon consumption of the starting material, as judged by TLC, the solution was partitioned between EtOAc and water. The water layer was basified to pH 12 with solid NaOH. The organic layer was then collected, dried over Na2SO4, filtered and concentrated to a residue that without further delay was dissolved in DMSO (5 mL). The mixture was then treated with 4-fluoro ethyl benzoate (550 mg, 3.28 mmol), diisopropyl ethyl amine (3 mL) and a catalytic amount of DMAP and heated at 120° C. in a sealed tube for 4 days. The reaction mixture was then cooled, partitioned between EtOAc and water. The EtOAc layer was collected dried over Na2SO4 filtered and concentrated to a solid that after suspension in CH2Cl2 and filtration afforded the product (100 mg, Yield: 53%). HRMS m/z calcd for C28H29N2O3I [M+H]+: 569.1296. Found: 569.1294.

Provenance & Evidence