반응 #742298
ord-2a961c3ea08944c1b8444fde543c17cf
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시약
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후처리
- 1온도to warm to room temperature
- 2온도heated at 80° C. overnight
- 3온도to cool to room temperature
- 4workup.STIRRINGto stir for 2 hours
- 5기타The organic layer was separated
- 6추출the aqueous was extracted with ethyl acetate (75 mL)
- 7세척The combined organics were washed with brine (75 mL)
- 8건조dried (MgSO4)
- 9여과filtered
- 10기타evaporated
- 11기타The crude product was purified by flash silica chromatography
- 12세척eluting with 20 to 50% ethyl acetate in isohexane
- 13기타This was further purified by flash silica chromatography
- 14세척eluting with 0 to 10% methanol in dichloromethane
실험 절차
Trimethylaluminium (6.22 mL, 12.44 mmol) was added to 5-methylpyrazin-2-amine (1.357 g, 12.44 mmol) in anhydrous toluene (20 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes. (S)-methyl 3-(3-(tert-butyldimethyl-silyloxy)azetidin-1-yl)-2-hydroxypropanoate (Intermediate AD3) (2 g, 6.91 mmol) in anhydrous toluene (10 mL) was added and the resulting solution was allowed to warm to room temperature and then heated at 80° C. overnight. The reaction was allowed to cool to room temperature and a solution of Rochelle salt in water (20%, 75 ml) was added. The mixture diluted with water (25 mL) and ethyl acetate (75 mL) and allowed to stir for 2 hours. The organic layer was separated and the aqueous was extracted with ethyl acetate (75 mL). The combined organics were washed with brine (75 mL), dried (MgSO4), filtered and evaporated. The crude product was purified by flash silica chromatography, eluting with 20 to 50% ethyl acetate in isohexane. This was further purified by flash silica chromatography, eluting with 0 to 10% methanol in dichloromethane, to afford the product (1.50 g, 59.2%). 1H NMR (400 MHz, CDCl3) δ 0.03 (3H, d), 0.04 (3H, s), 0.87 (9H, q), 2.54 (3H, s), 2.93 (2H, d), 3.09 (2H, q), 3.71-3.77 (2H, m), 4.04 (1H, t), 4.46 (1H, t), 8.13 (1H, d), 9.39 (1H, d), 9.81 (1H, s); m/z (ES+) (M+H)+=367.34; HPLC tR=1.76 min.