Potassium Carbonate → 3-Chloro-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridine

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Reaction Steps

To 5-chloro-3-((1-t-butoxycarbonyl-2-(S)-pyrrolidinyl)methoxy)pyridine (0.600 g, 1.92 mmol), from Example 15b, was added a solution of formic acid/formaldehyde (1:2, 3 mL). The mixture was heated at reflux for 3 hours, then basified with sat. K2CO3. The aqueous phase was extracted with CH2Cl2 (3×) then the organic layer was dried (MgSO4) and concentrated. The crude product was purified by chromatography over silica gel eluted with CHCl3/MeOH to afford 0.274 g (63%) of the title compound as a pale yellow oil. TLC Rf =0.23 (10%MeOH/CHCl3). MS (DCI/NH3) m/e: 227 (M+H)+ with 35Cl and 229 (M+H)+ with 37Cl. 1H NMR (CDCl3, 300 MHz) δ: 8.22 (d, J=2.6 Hz, 1H), 8.19 (d, J=2.2 Hz, 1H), 7.22 (t, J=2 Hz, 1H), 4.00 (dd, J=9, 5.50 Hz, 1H), 3.92 (dd, J=9, 5.20 Hz, 1H), 3.14-3.08 (m, 1H), 2.69-2.64 (m, 1H), 2.47 (s, 3H), 2.36-2.27 (m, 1H), 2.07-1.97 (m, 1H), 1.88-1.69 (m, 3H).

Provenance & Evidence