反应详情

n-butyllithium (13.3 mL of a 1.6 M solution in hexanes,21.3 mmol) was added to a solution of (2S)-2,5-dihydro-3,6-diethoxy-2-isopropyl pyrazine (Schöllkopf reagent)(4.30 g, 20.3 mmol) in tetrahydrofuran (THF) over the course of five minutes. The solution was maintained at −78° C. for 15 minutes after which 1,4-dibromobutane (9.75 mL, 81.2 mmol) was added in a single portion. After 2.5 hours at −78° C. the reaction was allowed to warm to room temperature and diluted with diethyl ether (100 mL). The organic phase was washed with water (100 mL), brine (100 mL) and then dried with magnesium sulfate (MgSO4). Following filtration and concentration most of the residual 1,4-dibromobutane was removed under high vacuum. The remaining oil was purified by silica gel chromatography (2% ethyl acetate in hexanes) to provide 5 (3.7 g, 57%) as a colorless liquid;[α]25D−1.13° (c=4.5, CHCl3); IR (thin film) 2957, 1689, 1456, 1364, 1304, 1230, 1144, 1038 cm−1; 1H NMR(300 MHz, CDCl3) δ4.04-4.18 (m, 4H) 3.94-4.02 (m, 1H) 3.90 (t, J=3.9, 1H) 3.39 (t, J=6.9, 2H) 2.21-2.32 (m, 1H) 1.68-1.92 (m, 4H) 1.33-1.47 (m, 2H) 1.274 (t, J=7.2, 3H) 1.268 (t, J=7.2, 3H) 1.03 (d, J=6.9, 3H) 0.70 (d, J=6.9, 3H); 13C NMR (100.6 MHz, CDCl3) d 163.12, 163.05, 60.72, 60.48, 55.09, 33.60, 33.11, 32.66, 31.80, 23.22, 19.03, 16.6, 14.34, 14.31; Mass Spectrum (FAB+) 347.1 (MH+).

1. additionwas added in a single portion
2. washThe organic phase was washed with water (100 mL), brine (100 mL)
3. dry with materialdried with magnesium sulfate (MgSO4)
4. filtrationfiltration and concentration most of the residual 1,4-dibromobutane
5. customwas removed under high vacuum
6. customThe remaining oil was purified by silica gel chromatography (2% ethyl acetate in hexanes)