Methyl iodide → HCID 9979960, compound

Participants

Reaction Steps

To 100 mg (0.22 mmol) of chloroformate 6-1 in THF was added 130 mg (0.65 mmol) of (+/−)-3-amino-1-N-Boc-piperidine (9-1) and 90 μL (0.65 mmol) of triethylamine. After stirring overnight at room temperature, the mixture was partitioned between EtOAc and saturated NaHCO3, the layers were separated, the organic phase was washed with water, brine, dried over MgSO4, and concentrated by rotary evaporation. The residue was purified by column chromatography on silica gel with EtOAc/hexanes to provide both diastereomers in pure form. To 35 mg (0.057 mmol) of the first eluting diastereomer in DMF at 0° C. was added 18 μL (0.29 mmol) of MeI and 11 mg (0.29 mmol) of NaH (60% dispersion in oil). After stirring for 3 h at 0° C., the reaction was quenched with saturated NH4Cl, poured into EtOAc, and the layers were separated. The organic phase was washed with brine, dried over MgSO4, and concentrated by rotary evaporation. The residue was then dissolved in CH2Cl2 and 1 mL of trifluoroacetic acid was added. After stirring for 3 h at room temperature, the solvents were removed, the residue was partitioned between EtOAc and saturated NaHCO3, the organic phase was washed with brine, dried over MgSO4 and concentrated by rotary evaporation. The residue was then purified by silica gel chromatography with 20:1:1 EtOH/NH4OH/H2O in EtOAc to provide 9-2 as a white solid. Data for 9-2: 1HNMR (500 MHz, CDCl3) δ 7.4-7.2 (m, 5H), 7.1-6.9 (m, 3H), 6.25 (s, 1H), 4.8 (m, 1H), 4.65 (m, 1H), 4.45 (m, 1H), 4.0 (m, 1H), 3.8 (m, 1H), 3.1 (m, 2H) 2.9 (s, 3H), 2.6 (m, 2H), 2.1-0.9 (m, 6H) ppm. HRMS (ES) calc'd M+H for C24H27F2N3O2: 428.2144. Found: 428.2132.

Provenance & Evidence