Hydrochloric Acid → 3-((1-methyl-2-(R)-piperidinyl)methoxy)pyridine dihydrochloride

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The compound from step 42b (553 mg, 4.28 mmol) was allowed to react with 3-bromopyridine (0.43 mL, 4.50 mmol), cuprous bromide (0.165 g, 0.86 mmol), triphenylphosphine (0.449 g, 1.7 mmol) and potassium carbonate (0.592 g, 4.28 mmol). The reaction mixture was heated to 90° C. and stirred for 120 hr, then cooled to 25° C., acidified with HCl (1.5 M; 35 mL) and washed with ethyl acetate (4×50 mL). The aqueous layer was basified with saturated aqueous potassium carbonate, and the product was extracted with chloroform (6×50 mL), dried (MgSO4) and concentrated in vacuo to an oil. The crude product was purified by chromatography on silica gel (CH2Cl2 /EtOAc/MeO/HNH4OH 50:50:4:1) to yield the free base of the title compound (0.048 g). The amine was treated as in example 1b to yield the title compound as a hygroscopic semisolid (0.024 g, 2%). MS (DCI/NH3) m/e: 207 (M+H)+. 1H NMR (D2O, 300 MHz) δ: 8.37-8.29 (m, 2H), 7.66 (dd, J=8.45, 1.5 Hz, 1H), 7.59-7.57 (m, 1H), 4.63 (dt, J=14.5, 2.4 Hz, 2H), 4.8 (dd, J=11.9, 1.8 Hz, 1H), 3.58-3.53 (m, 2H), 3.20 (m, 1H), 2.93 (s, 3H), 2.05-1.60 (m, 5H). Anal. calc. for C12H20Cl2N2O.2.0 H2O: C, 45.72; H, 7.67; N, 8.89. Found: C, 45.82; H, 7.93; N, 8.84. [α]D23 -1.14° (c=0.71 in MeOH).

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