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0 °C

Bicyclic alcohol 43 (4.2 g, 11.59 mmol) and 4-fluoro-benzyl bromide (2.2 mL, 17.4 mmol) were dissolved in DMF (115 mL) and cooled to 0° C. Sodium hydride (930 mg, 23.2 mmol) was added and, after ˜5 min, the ice bath was removed. After 15 min, the reaction mixture was diluted with toluene (250 mL) and saturated aqueous NH4Cl (500 mL) and extracted with 1:1 Et2O/hexanes (600 mL). The organic layer was washed successively with 1N HCl, water, saturated aqueous NaHCO3, water, and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by flash silica gel chromatography (10:1 to 1:1 hexanes/EtOAc) to afford 5.15 g of 44 as a viscous oil (94%): 1H NMR (300 MHz, CDCl3): δ7.36 (m, 6H), 7.07-6.92 (m, 3H), 5.15 (m, 2H), 4.63 (m, 1H), 4.50 (m, 1H), 4.32 (m, 1H), 4.19 (m, 1H), 3.97 (m, 1H), 3.87-3.64 (m, 2H), 3.25-3.08 (m, 2H), 2.35 (m, 0.5H), 2.17 (m, 0.5H), 1.88 (m, 1H), 1.46 (s, 9H) ppm. Mass spectrum, m/z [414.7] (M−t-Bu)+.

1. customthe ice bath was removed
2. additionthe reaction mixture was diluted with toluene (250 mL) and saturated aqueous NH4Cl (500 mL)
3. extractionextracted with 1:1 Et2O/hexanes (600 mL)
4. washThe organic layer was washed successively with 1N HCl, water, saturated aqueous NaHCO3, water, and brine
5. dry with materialdried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude product was purified by flash silica gel chromatography (10:1 to 1:1 hexanes/EtOAc)