Reaction Steps
A slurry of (S)-1-(1-chloro-3-methylnaphthalen-2-yl)-2-(trityloxy)ethanol (10.8 grams, 22.5 mmol) and DMF (40 mL) was treated with NaH (60% w/w in mineral oil, 11.3 mmol) at 23° C. After 5 min, ethyl-(2-bromovalerate) (1.65 mL, 11.3 mmol) was added. After 30 min had passed, more NaH (60% w/w in mineral oil, 11.3 mmol) was added. After stirring for 5 min, additional ethyl-(2-bromovalerate) (1.65 mL, 11.3 mmol) was added. Again, after 30 min had passed, more NaH (60% w/w in mineral oil, 11.3 mmol) was added. After stirring for 5 min, additional ethyl-(2-bromovalerate) (1.65 mL, 11.3 mmol) was added. Once more, after 30 min had passed, more NaH (60% w/w in mineral oil, 11.3 mmol) was added. After stirring for 5 min, additional ethyl-(2-bromovalerate) (1.65 mL, 11.3 mmol) was added. The reaction was stirred for another hour. Saturated aq. NH4Cl (100 mL) was added, followed by H2O (100 mL). After stirring for 10 min, the reaction was extracted with EtOAc (200 mL). The organic extract was washed with 5% w/v aq. LiCl (3×100 mL). The final organic phase was dried over Na2SO4, filtered, and concentrated. The residue was treated with benzene and purified by flash column chromatography (silica gel, 0 to 20% ethyl acetate/hexanes) to give (S)-ethyl 2-(1-(1-chloro-3-methylnaphthalen-2-yl)-2-(trityloxy)ethoxy)-2-methylpropanoate. 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J=8.6 Hz, 1H), 7.70 (d, J=8.2 Hz, 1H), 7.57-7.38 (m, 2H), 7.49 (s, 1H), 7.36-7.32 (m, 6H), 7.21-7.14 (m, 9H), 5.94 (dd, J=6.7, 6.7 Hz, 1H), 3.93-3.74 (m, 2H), 3.61 (dd, J=9.0, 7.0 Hz, 1H), 3.33 (dd, J=9.0, 5.3 Hz, 1H), 2.52 (s, 3H), 1.46 (s, 3H), 1.37 (s, 3H), 0.99 (dd, J=7.0, 7.0 Hz, 3H). Additionally, starting material ((S)-1-(1-chloro-3-methylnaphthalen-2-yl)-2-(trityloxy)ethanol) was recovered. Yield was not determined.
