2,2,2-Trifluoroethyl trifluoromethanesulfonate → (4-Isopropoxy-3-methyl-phenyl)-[10-(5-methyloxazol-2-yl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone

Participants

Reaction Conditions

Reaction Steps

A mixture of (4-isopropoxy-3-methyl-phenyl)-[10-(3-methyl-1,2,4-oxadiazol-5-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone hydrochloride salt (28 mg, 0.06 mmol), 2,2,2-trifluoroethyl trifluoromethanesulfonate (14 μL, 0.09 mmol) and NaHCO3 (21 mg, 0.23 mmol) was heated at 80° C. in a sealed vial for 18 hours. The reaction mixture was allowed to cool to room temperature, microfiltered and purified by Waters mass directed LC/MS: (10-99% ACN/H2 0 (5 mM HCl)) and concentrated to yield (4-isopropoxy-3-methyl-phenyl)-[10-(5-methyloxazol-2-yl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone (3 mg, 10%) as a white solid. ESI-MS m/z calc. 496.5. Found 497.7 (M+1)+; Retention time: 1.99 minutes (3 min run); 1H NMR (400 MHz, DMSO) δ 7.27-7.06 (m, 2H), 6.96 (d, J=9.1 Hz, 1H), 5.17 (dd, J=13.6, 4.2 Hz, 1H), 4.63 (dt, J=12.1, 6.2 Hz, 1H), 3.31-3.19 (m, 5H), 2.92-2.81 (m, 1H), 2.67 (dd, J=12.0, 10.1 Hz, 1H), 2.43-2.27 (m, 6H), 2.15 (s, 3H), 1.70-1.40 (m, 4H), 1.29 (d, J=6.0 Hz, 6H).

Provenance & Evidence