反应详情

To a solution of 1-methyl-cyclopropanecarbaldehyde (1.85 g, 22.0 mmol) in CHCl3 (30 mL) was added (S)-2-amino-2-phenylethanol (2.74 g, 20.0 mmol) and MgSO4 (3 g). The cloudy reaction mixture was stirred at room temperature for 3 hr then filtered, rinsing with CHCl3 (10 mL). Cooled to 0° C. and slowly added trimethylsilanecarbonitrile (5.0 ml, 39.9 mmol). The orange reaction mixture was stirred at 0° C. for 1 hr then allowed to warm to room temperature overnight. The reaction was quenched with 1.0 M HCl and stirred vigorously for 5 min then neutralized with 10% aqueous NaOH and extracted with CH2Cl2. The combined organics were dried over MgSO4 and concentrated to a light orange oil. NMR analysis showed that some TMS-ether remained. The crude product was treated with 10 mL of 3.0 M aqueous HCl for 10 min at which time TLC verified that the silyl group was removed. Extracted with CH2Cl2 (2×), dried over MgSO4 and concentrated. The residue was purified by SiO2 chromatography (10-30% EtOAc/hexanes) to isolate 1.0 g (22%) of (R)-2-((S)-2-hydroxy-1-phenylethylamino)-2-(1-methylcyclopropyl)acetonitrile as a colorless oil and a single diastereomer.

1. customThe cloudy reaction mixture
2. filtrationthen filtered
3. washrinsing with CHCl3 (10 mL)
4. temperatureCooled to 0° C.
5. stirringThe orange reaction mixture was stirred at 0° C. for 1 hr
6. temperatureto warm to room temperature overnight
7. customThe reaction was quenched with 1.0 M HCl
8. stirringstirred vigorously for 5 min
9. extractionextracted with CH2Cl2
10. dry with materialThe combined organics were dried over MgSO4
11. concentrationconcentrated to a light orange oil
12. additionThe crude product was treated with 10 mL of 3.0 M aqueous HCl for 10 min at which time TLC
13. customwas removed
14. extractionExtracted with CH2Cl2 (2×)
15. dry with materialdried over MgSO4
16. concentrationconcentrated
17. customThe residue was purified by SiO2 chromatography (10-30% EtOAc/hexanes)