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

HRID 1477504

반응식

HRID 1477504 반응식
[C:1]12([C:7]3[O:11][N:10]=[C:9]([CH3:12])[N:8]=3)[CH2:6][CH:5]1[CH2:4][NH:3][CH2:2]2.C(=O)(O)[O-].[Na+].[Cl-].[Na+].C(O)(=O)[C@H]([C@@H](C(O)=O)O)O>O.CO>[C@@:1]12([C:7]3[O:11][N:10]=[C:9]([CH3:12])[N:8]=3)[CH2:6][C@@H:5]1[CH2:4][NH:3][CH2:2]2

참가 물질

7

반응물 4

HCID 5234Sodium ChlorideHCID 439655D-Tartaric acidHCID 516892Sodium BicarbonateHCID 533270125-(3-Azabicyclo[3.1.0]hexan-1-yl)-3-methyl-1,2,4-oxadiazole

생성물 1

HCID 866993145-((1S,5S)-3-azabicyclo[3.1.0]hexan-1-yl)-3-methyl-1,2,4-oxadiazole수율 58.2%

시약·촉매·용매 2

HCID 887Methanol용매HCID 962Water용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-94c1ddae35074de78805b3bd4cd79d98
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09403806B1

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