反应详情

HCl (781 μL of 4 M in dioxane, 3.12 mmol) was added to a solution of tert-butyl 4-(2,2-difluoroethyl)-2-(oxazol-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate (121 mg, 0.31 mmol) in DCM (0.7 mL) and the reaction mixture was stirred for 1 hour at room temperature. The solvent and excess HCl was removed under reduced pressure and the resulting solid was dissolved in methanol (3 mL) and purified by Waters mass directed LC/MS: (1-99% ACN/H2O (5 mM HCl)). The desired fractions were combined and concentrated in vacuo to yield 4-(2,2-difluoroethyl)-2-(oxazol-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecane hydrochloride salt (95 mg, 94%) as a white solid. ESI-MS m/z calc. 287.1. Found 288.3 (M+1)+; Retention time: 0.96 minutes (3 min run); 1H NMR (400 MHz, DMSO) δ 8.15 (d, J=0.8 Hz, 1H), 7.23 (d, J=0.8 Hz, 1H), 6.22 (tt, J=55.1, 4.0 Hz, 1H), 4.94 (dd, J=10.8, 2.6 Hz, 1H), 3.19-2.79 (m, 8H), 2.65-2.54 (m, 2H), 2.25 (dd, J=11.9, 1.5 Hz, 1H), 1.83-1.70 (m, 2H), 1.65 (dd, J=15.1, 3.9 Hz, 1H).

1. customThe solvent and excess HCl was removed under reduced pressure
2. dissolutionthe resulting solid was dissolved in methanol (3 mL)
3. custompurified by Waters mass
4. concentrationconcentrated in vacuo