反应详情

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.

1. waitAfter 30 min had passed
2. waitAgain, after 30 min had passed
3. stirringAfter stirring for 5 min
4. waitOnce more, after 30 min had passed
5. stirringAfter stirring for 5 min
6. stirringThe reaction was stirred for another hour
7. stirringAfter stirring for 10 min
8. extractionthe reaction was extracted with EtOAc (200 mL)
9. extractionThe organic extract
10. washwas washed with 5% w/v aq. LiCl (3×100 mL)
11. dry with materialThe final organic phase was dried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated
14. additionThe residue was treated with benzene
15. custompurified by flash column chromatography (silica gel, 0 to 20% ethyl acetate/hexanes)