Reaction Steps
To ((1S,2S)-2-(5-bromo-2-(cyclopropylmethoxy)phenyl)cyclopropyl)methanol (S8) (2.15 g, 7.23 mmol, 1.00 equiv) in CH2Cl2 (30 mL) in an oven-dried round-bottom flask under a N2 atmosphere at 0 ° C. was added Et3N (2.20 g, 3.03 mL, 21.7 mmol, 3.00 equiv) and MsCl (1.66 g, 1.13 mL, 14.5 mmol, 2.00 equiv). The reaction mixture was stirred at 0 ° C. for 2 hours. The reaction mixture turned yellow and a precipitate formed. The reaction mixture was poured into a separatory funnel with saturated NH4Cl solution (40 mL). The funnel was shaken and the organic phase collected. The aqueous phase was extracted from with diethyl ether (3×75 mL). The organic phases were combined and washed with saturated NaHCO3 (100 mL) and brine (100 mL), dried with MgSO4, and concentrated in vacuo. The residue was dissolved in DMF (30 mL) and NaN3 (1.88 g, 28.9 mmol, 4.00 equiv) was added. The reaction mixture was heated at 60 ° C. for 1 hour. The reaction mixture was cooled and poured into 60 mL of water. The reaction mixture was extracted from with diethyl ether (3×75 mL). The combined organic phases were washed with brine (100 mL), dried with MgSO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel, eluting with a gradient of 5-10% EtOAc in hexanes (v/v) to afford 1.95 g of the title compound as a colorless oil (84% yield). Rf=0.60 (hexanes/EtOAc 19:1 (v/v)). NMR Spectroscopy: 1H NMR (500 MHz, CDCl3, 23 ° C., δ): 7.21 (dd, J=8.7, 2.3 Hz, 1H), 6.96 (d, J=2.3 Hz, 1H), 6.66 (d, J=8.7 Hz, 1H), 3.84-3.78 (m, 2H), 3.40 (dd, J=12.8, 6.4, 1H), 3.24 (dd, J=12.8, 7.1 Hz, 1H), 2.11 (ddd, J=8.7, 5.0, 5.0 Hz, 1H), 1.38-1.32 (m, 1H), 1.31-1.25 (m, 1H), 1.08-1.04 (m, 1H), 0.98-0.94 (m, 1H), 0.68-0.58 (m, 2H), 0.40-0.31 (m, 2H). 13C NMR (125 MHz, CDCl3, 23 ° C., δ): 156.9, 132.8, 129.5, 128.8, 113.4, 112.9, 73.3, 55.3, 20.8, 16.2, 12.8, 10.4, 3.3, 3.2. HRMS-FIA (m/z): calcd for C14H16BrN3NaO [M+Na]+, 344.0374; found, 344.0363.
