تفاعل #742298

معادلة التفاعل

Trimethylaluminium

5-methylpyrazin-2-amine

Rochelle salt

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

→

product

المردود 59.2%

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

المردود 59.2%

المذيبات

toluene

water

toluene

water

ethyl acetate

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةto warm to room temperature
2. 2
   درجة الحرارةheated at 80° C. overnight
3. 3
   درجة الحرارةto cool to room temperature
4. 4
   workup.STIRRINGto stir for 2 hours
5. 5
   أخرىThe organic layer was separated
6. 6
   استخلاصthe aqueous was extracted with ethyl acetate (75 mL)
7. 7
   غسيلThe combined organics were washed with brine (75 mL)
8. 8
   تجفيفdried (MgSO4)
9. 9
   ترشيحfiltered
10. 10
    أخرىevaporated
11. 11
    أخرىThe crude product was purified by flash silica chromatography
12. 12
    غسيلeluting with 20 to 50% ethyl acetate in isohexane
13. 13
    أخرىThis was further purified by flash silica chromatography
14. 14
    غسيلeluting with 0 to 10% methanol in dichloromethane

الإجراء التجريبي

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.

المصدر