Trifluoroacetic acid → HCID 69619565, compound

Participants

Reaction Conditions

Reaction Steps

2-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-4-methyl-piperidine-1-carboxylic acid tert-butyl ester (320 mg, 33.9%) was prepared according to the procedure in Example 25 from 4-methyl-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester (607.5 mg, 2.5 mmol), triethylamine (1.01 g, 10 mmol) with isobutyl chloroformate (348 mg, 2.55 mmol) in THF (5 mL). After 30 minutes, 3-Chloro-N-hydroxy-benzamidine (425 mg, 2.5 mmol) in DMF (4 mL) was added and the mixture was heated to 130° C. for 4 h. The product was purified by column chromatography with 10% ethyl acetate in hexanes. Deprotection was carried out according to the procedure in Example 39 from 2-[3-(3-chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-4-methyl-piperidine-1-carboxylic acid tert-butyl ester(320 mg, 0.847 mmol) with trifluoroacetic acid (1.3 ml) and dichloromethane(10 mL) for 3 h. Purification by column chromatography with 50/50 ethyl acetate/hexanes gave trans-2-[3-(3-chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-4-methyl-piperidine 164.8 mg (70%); 1H-NMR(CDCl3) 6(ppm): 8.10 (s, 1H), 7.97 (d, 1H), 7.42 (m, 2H), 4.07 (d, 1H), 3.26 (dd, 1H), 2.80 (t, 1H), 2.17 (d, 1H), 1.99 (w, 1H), 1.69 (m, 2H), 1.24 (m, 2H) and 1.02 (d, 3H), and cis-2-[3-(3-chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-4-methyl-piperidine 23.9 mg(10.2%); 1H-NMR(CDCl3) 8(ppm): 8.10 (s, 1H), 7.97 (d, 1H), 7.43 (m, 2H), 4.45 (t, 1H), 2.93 (m, 2H), 2.24(m, 2H), 2.68 (m, 3H), 1.29 (m, 1H) and 0.99 (d, 3H).

Provenance & Evidence