Reaktion #742298

Reaktionsgleichung

Trimethylaluminium

5-methylpyrazin-2-amine

Rochelle salt

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

→

product

Ausbeute 59.2%

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

Ausbeute 59.2%

Lösungsmittel

toluene

water

toluene

water

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto warm to room temperature
2. 2
   Temperaturheated at 80° C. overnight
3. 3
   Temperaturto cool to room temperature
4. 4
   workup.STIRRINGto stir for 2 hours
5. 5
   SonstigeThe organic layer was separated
6. 6
   Extraktionthe aqueous was extracted with ethyl acetate (75 mL)
7. 7
   WaschenThe combined organics were washed with brine (75 mL)
8. 8
   Trocknendried (MgSO4)
9. 9
   Filtrationfiltered
10. 10
    Sonstigeevaporated
11. 11
    SonstigeThe crude product was purified by flash silica chromatography
12. 12
    Wascheneluting with 20 to 50% ethyl acetate in isohexane
13. 13
    SonstigeThis was further purified by flash silica chromatography
14. 14
    Wascheneluting with 0 to 10% methanol in dichloromethane

Vorschrift

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.

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