Sodium Chloride → 5-((1S,5S)-3-azabicyclo[3.1.0]hexan-1-yl)-3-methyl-1,2,4-oxadiazole

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Reaction Steps

5-(3-Azabicyclo[3.1.0]hexan-1-yl)-3-methyl-1,2,4-oxadiazole (105) (923 mg, 4.58 mmol) was dissolved in water (20 mL) and treated with saturated sodium bicarbonate (40 mL), and 5 g of sodium chloride (pH=8). The aqueous layer was extracted with dichloromethane (6×100 mL), the organic layers combined, dried over magnesium sulfate and filtered through a fritted glass filter. The filtrate was treated with D-tartaric acid (655 g, 4.36 mmol) in 60 mL of methanol and evaporated to dryness. The solid residue was dissolved in 6 mL of methanol and then 23 mL of acetonitrile were added. An oily residue that formed was decanted away from and dried under vacuum. The crude solid was dissolved into a minimal amount of boiling methanol (40 mL) and then acetonitrile (100 mL, 2.5:1, acetonitrile to methanol ratio) was added. The mixture was allowed to stir at room temperature for 20 minutes prior to isolation. The process was repeated until the crystalline substance exceeded an enantiomeric purity of 99.5%; obtained 440 mg of 5-((1S,5S)-3-azabicyclo[3.1.0]hexan-1-yl)-3-methyl-1,2,4-oxadiazole (106b). The optical purity was determined by HPLC analysis (Chiral Technologies Chiral-AGP, 4.0 mm×150 mm, 0.5% methanol, 20 mM sodium phosphate pH=7). (106b) MS (ESI) m/z 165.8 [M+H]+. 1H NMR (DMSO-d6) δ: 1.44 (m, 2H), 2.23 (m, 1H), 2.28 (s, 3H)m, 3.06 (s, 2H), 3.35 (m, 2H), 4.13 (s, 2H).

Provenance & Evidence