Sulfuric acid magnesium salt (1:1) → (R)-2-((S)-2-hydroxy-1-phenylethylamino)-2-(1-methylcyclopropyl)acetonitrile

Participants

Reaction Steps

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.

Provenance & Evidence