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

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 (pH8). 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), 3.06 (s, 2H), 3.35 (m, 2H), 4.13 (s, 2H).

1. extractionThe aqueous layer was extracted with dichloromethane (6×100 mL)
2. dry with materialdried over magnesium sulfate
3. filtrationfiltered through a fritted glass
4. filtrationfilter
5. customevaporated to dryness
6. dissolutionThe solid residue was dissolved in 6 mL of methanol
7. addition23 mL of acetonitrile were added
8. customAn oily residue that formed
9. customwas decanted away from and
10. customdried under vacuum
11. dissolutionThe crude solid was dissolved into a minimal amount of boiling methanol (40 mL)
12. additionacetonitrile (100 mL, 2.5:1, acetonitrile to methanol ratio) was added

ORDレコード

ord-ffcf65b0e67a4288a541c122a85c47cc

出典データセット

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09174972B2