Triethylamine → Mirogabalin

HRID 551682노트

반응식

HRID 551682 반응식
C([O:5][C:6](=[O:21])[CH2:7][C@@:8]1([CH2:17][N+:18]([O-])=O)[CH2:14][C@@H:13]2[C@H:9]1[CH:10]=[C:11]([CH2:15][CH3:16])[CH2:12]2)(C)(C)C.[Cl-].[NH4+].CC(OC(OC(OC(C)(C)C)=O)=O)(C)C.C(N(CC)CC)C>C(O)C.O.ClCCl.[Fe]>[NH2:18][CH2:17][C@:8]1([CH2:7][C:6]([OH:21])=[O:5])[CH2:14][C@@H:13]2[C@H:9]1[CH:10]=[C:11]([CH2:15][CH3:16])[CH2:12]2

참가 물질

9

반응물 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 90495Di-tert-butyl dicarbonateHCID 91092873tert-butyl 2-((1R,5S,6S)-3-ethyl-6-(nitromethyl)bicyclo[3.2.0]hept-3-en-6-yl)acetate

생성물 1

HCID 59509752Mirogabalin

시약·촉매·용매 4

HCID 23925Iron촉매HCID 702Ethanol용매HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

Tert-butyl[(1R,5S,6S)-3-ethyl-6-(nitromethyl)bicyclo[3.2.0]hept-3-en-6-yl]acetate (peak 1, 7.0 g, 23.7 mmol) was dissolved in ethanol (60 mL) and water (21 mL). To the solution, iron powder (13.27 g, 237 mmol) and ammonium chloride (628.1 mg, 11.9 mmol) were added, and the mixture was stirred for 5.5 hours under heating to reflux. The mixture was allowed to cool, then diluted with saturated saline, a saturated aqueous solution of sodium bicarbonate, and ethyl acetate, and filtered through Celite to remove insoluble matter. The filtrate was separated into organic and aqueous layers. The organic layer was washed with saturated saline and then dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure to obtain a pale yellow oil substance (7.02 g). This substance was dissolved in dichloromethane (200 mL). To the solution, (Boc)2O (5.25 g, 25 mmol) and triethylamine (5.01 g, 50 mmol) were added, and the mixture was stirred overnight at room temperature. The solvent was distilled off under reduced pressure, and the residue was then purified by silica gel chromatography to obtain the title compound of interest as a pale yellow oil substance (8.82 g, <100%).

후처리

  1. temperatureunder heating to reflux
  2. temperatureto cool
  3. additiondiluted with saturated saline
  4. filtrationa saturated aqueous solution of sodium bicarbonate, and ethyl acetate, and filtered through Celite
  5. customto remove insoluble matter
  6. customThe filtrate was separated into organic and aqueous layers
  7. washThe organic layer was washed with saturated saline
  8. dry with materialdried over anhydrous magnesium sulfate
  9. distillationThen, the solvent was distilled off under reduced pressure
  10. customto obtain a pale yellow oil substance (7.02 g)
  11. stirringthe mixture was stirred overnight at room temperature
  12. distillationThe solvent was distilled off under reduced pressure
  13. customthe residue was then purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-9fe9e84a49de461f8c3bbd97878c6f69
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07947738B2

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