反应详情

温度

0 °C

Trimethylaluminium (2M in hexane) (1.126 mL, 2.25 mmol) was added dropwise to 5-methylpyrazin-2-amine (214 mg, 1.96 mmol) in toluene (5 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred for 20 minutes. A solution of (S)-methyl 2-(tert-butyldimethylsilyloxy)-3-((S)-1-methoxypropan-2-yloxy)propanoate (Intermediate Y1) (600 mg, 1.96 mmol) in toluene (2 mL) was added to the reaction mixture and the resulting solution was stirred at reflux for 5 hours. The reaction was allowed to cool to RT before adding ethyl acetate (30 mL) and 20% sodium potassium tartrate solution (30 mL), which was stirred vigorously for 16 hours. The phases were separated and the organic layer was washed with sat. brine (15 mL), dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 0 to 60% ethyl acetate in isohexane to afford the product (230 mg, 31%). 1H NMR (400 MHz, CDCl3) 6 0.17 (d, 6H), 0.98 (s, 9H), 1.16 (d, 3H), 2.53 (s, 3H), 3.25-3.32 (m, 4H), 3.35-3.42 (m, 1H), 3.60-3.68 (m, 1H), 3.74-3.80 (m, 1H), 3.82-3.87 (m, 1H), 4.35-4.40 (m, 1H), 8.12-8.13 (m, 1H), 8.98 (s, 1H), 9.42 (d, 1H); m/z (ESI+) (M+H)+=384.23; HPLC tR=10.70 min.

1. stirringthe resulting solution was stirred
2. temperatureat reflux for 5 hours
3. temperatureto cool to RT
4. stirringwas stirred vigorously for 16 hours
5. customThe phases were separated
6. washthe organic layer was washed with sat. brine (15 mL)
7. dry with materialdried (MgSO4)
8. customevaporated
9. customThe crude product was purified by flash silica chromatography
10. washeluting with 0 to 60% ethyl acetate in isohexane