Reaktion #1985708

Reaktionsgleichung

trimethylsilanecarbonitrile

1-methyl-cyclopropanecarbaldehyde

(S)-2-amino-2-phenylethanol

MgSO4

→

(R)-2-((S)-2-hydroxy-1-phenylethylamino)-2-(1-methylcyclopropyl)acetonitrile

Ausbeute 22.0%

Lösungsmittel

CHCl3

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe cloudy reaction mixture
2. 2
   Filtrationthen filtered
3. 3
   Waschenrinsing with CHCl3 (10 mL)
4. 4
   TemperaturCooled to 0° C.
5. 5
   workup.STIRRINGThe orange reaction mixture was stirred at 0° C. for 1 hr
6. 6
   Temperaturto warm to room temperature overnight
7. 7
   SonstigeThe reaction was quenched with 1.0 M HCl
8. 8
   workup.STIRRINGstirred vigorously for 5 min
9. 9
   Extraktionextracted with CH2Cl2
10. 10
    TrocknenThe combined organics were dried over MgSO4
11. 11
    Einengenconcentrated to a light orange oil
12. 12
    workup.ADDITIONThe crude product was treated with 10 mL of 3.0 M aqueous HCl for 10 min at which time TLC
13. 13
    Sonstigewas removed
14. 14
    ExtraktionExtracted with CH2Cl2 (2×)
15. 15
    Trocknendried over MgSO4
16. 16
    Einengenconcentrated
17. 17
    SonstigeThe residue was purified by SiO2 chromatography (10-30% EtOAc/hexanes)

Vorschrift

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.

Quelle