反应 #742298

反应方程式

Trimethylaluminium

5-methylpyrazin-2-amine

Rochelle salt

(S)-methyl 3-(3-(tert-butyldimethyl-silyloxy)azetidin-1-yl)-2-hydroxypropanoate

→

product

收率 59.2%

(S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-hydroxy-N-(5-methylpyrazin-2-yl)propanamide

收率 59.2%

溶剂

toluene

water

toluene

water

ethyl acetate

反应条件

后处理

1. 1
   温度to warm to room temperature
2. 2
   温度heated at 80° C. overnight
3. 3
   温度to cool to room temperature
4. 4
   workup.STIRRINGto stir for 2 hours
5. 5
   其他The organic layer was separated
6. 6
   萃取the aqueous was extracted with ethyl acetate (75 mL)
7. 7
   洗涤The combined organics were washed with brine (75 mL)
8. 8
   干燥dried (MgSO4)
9. 9
   过滤filtered
10. 10
    其他evaporated
11. 11
    其他The crude product was purified by flash silica chromatography
12. 12
    洗涤eluting with 20 to 50% ethyl acetate in isohexane
13. 13
    其他This was further purified by flash silica chromatography
14. 14
    洗涤eluting with 0 to 10% methanol in dichloromethane

实验过程

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.

来源