Potassium Sodium Tartrate → 1-((5-Bromopyridin-3-yloxy)methyl)cyclopropanamine

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A dry, 10 mL round bottom flask was charged with 2-(5-bromopyridin-3-yloxy)acetonitrile (0.0996 g, 0.47 mmol), 3 mL dry THF, and a stirbar. The flask was fitted with an inert atmosphere inlet, and swept with Ar for several minutes. The solution was treated with titanium isopropoxide (0.15 ml, 0.51 mmol). To the stirring solution was added ethylmagnesium bromide 1.0 m solution in the (0.94 ml, 0.94 mmol) via a syringe pump over 30 minutes. The reaction was stirred at room temperature for 24 h after which time 1 mL of saturated Rochelle's salt was added, followed by 5 mL dry THF. The slurry was stirred/sonicated over the course of 1 h. The solution was then applied to 20 g of SiO2 wet packed with THF. The Silica was eluted with 75 mL dry THF, and the eluent was concentrated in vacuo. The crude was purified using a 19×150 mm Waters Xterra Prep C18 OBD column (100 Å pore diameter, 5 μm particle size, spherical shape, PN 186002381; Gradient: 0→5 min@20 mL/min, 10% B; 5.0→35 min@20 mL/min, linear gradient to 40% B; 35→45@20 mL/min, isocratic at 40% B, 45→55 min@20 mL/min, step to 100% B; 55→60 min@20 mL/min, step to 10% B; 60 min end; A=10.7 mM NH4HCO3 in water, pH adjusted to 8.6 with concentrated NH4OH; B acetonitrile). A band that eluted from 16.1 to 18.3 minutes was isolated. The solvent was removed in vacuo to afford 1-((5-bromopyridin-3-yloxy)methyl)cyclopropanamine (0.0214 g, 19% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 0.64-0.67 (m, 2H) 0.77-0.81 (m, 2H) 1.78 (br. s., 2H) 3.88 (s, 2H) 7.37 (dd, J=2.54, 1.86 Hz, 1H) 8.26 (d, J=2.54 Hz, 1H) 8.29 (d, J=1.86 Hz, 1H). 13C NMR (101 MHz, chloroform-d) δ ppm 12.89 (s, 2 C) 33.49 (s, 1 C) 77.00 (s, 1 C) 120.35 (s, 1 C) 124.03 (s, 1 C) 136.43 (s, 1 C) 143.07 (s, 1 C) 155.53 (s, 1 C). HPLC-MS: retention time=0.87 min (>99%@215 nm; >99% @254 nm; m/z=242.9, calculated for C9H1179BrN2O+H+=243.0; m/z=244.9, calculated for C9H1181BrN2O+H+=245.0).

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