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Mitsunobu

(Azide)







Examples:


Example 1



To a solution of the SM (48 g, 384 mmol) and PPh3 (121 g, 461 mmol) in THF (1.8 L) was added DIAD ( 93.1 g, 461 mmol). The reaction mixture was cooled to 10 C and treated with DPPA (98.8 g, 461 mmol). The mixture was stirred at RT for 16 h and then concentrated in vacuo. The crude was purified by flash chromatography (eluting with 33% EtOAc/pentane). The product fractions were concentrated to ~150 mL and diluted with EtOH (1.0 L). Added 10% Pd/C and hydrogenated the mixture under 1 atm of H2. Filtered the mixture and concentrated the filtrate in vacuo to a volume of ~500 mL.10M HCl (50 mL) was added dropwise and the resulting solid was filtered and washed with EtOH to provide the product as a solid. [30 g, 44%]. [WO2010032200]



Example 2



To a solution of the SM (3.1 g, 16.2 mmol) in THF (60 mL) at 0 C was added DIAD (6.3 mL, 32.0 mmol), PPh3 (8.52 g, 32.5 mmol), and DPPA (6.98 mL, 32.5 mmol). The reaction mixture was stirred at RT for 4.5 h. The mixture was quenched with H2O and extracted with EtOAc. The org layer was washed with brine (2x), dried (MgSO4), concentrated, and purified by silica gel column chromatography to provide the product as a yellow oil. [2.4 g, 68%] [WO2015129926, page 146]



Example 3



To a solution of PPh3 (317 mg, 1.21 mmol) in anhydrous THF (5 mL) at 0 C was added DIAD (224 mg, 1.11 mmol), followed by the SM (260 mg, 1.1 mmol), then DPPA (554 mg, 2.01 mmol). The reaction mixture was allowed to warm to RT and stir for 2 h. The mixture was diluted with ether and washed with sat aq NaHCO3, brine, dried (MgSO4), and concentrated. The resulting material was purified using a 12 g silica cartridge (15-25% acetone/heptane) to provide the product. [0.24 g, 84%] [WO2016011390, page 412]