Reacción #742298

Ecuación de reacción

Trimethylaluminium

5-methylpyrazin-2-amine

Rochelle salt

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

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product

Rendimiento 59.2%

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

Rendimiento 59.2%

Disolventes

toluene

water

toluene

water

ethyl acetate

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato warm to room temperature
2. 2
   Temperaturaheated at 80° C. overnight
3. 3
   Temperaturato cool to room temperature
4. 4
   workup.STIRRINGto stir for 2 hours
5. 5
   OtroThe organic layer was separated
6. 6
   Extracciónthe aqueous was extracted with ethyl acetate (75 mL)
7. 7
   LavadoThe combined organics were washed with brine (75 mL)
8. 8
   Secadodried (MgSO4)
9. 9
   Filtraciónfiltered
10. 10
    Otroevaporated
11. 11
    OtroThe crude product was purified by flash silica chromatography
12. 12
    Lavadoeluting with 20 to 50% ethyl acetate in isohexane
13. 13
    OtroThis was further purified by flash silica chromatography
14. 14
    Lavadoeluting with 0 to 10% methanol in dichloromethane

Procedimiento

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.

Fuente