Triethylamine → Mirogabalin

HRID 551682Notes

Reaction equation

HRID 551682 reaction equation
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

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 90495Di-tert-butyl dicarbonateHCID 91092873HCID 91092873, compound

Product 1

HCID 59509752Mirogabalin

Reagents, catalysts & solvents 4

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-9fe9e84a49de461f8c3bbd97878c6f69
Source dataset
uspto-grants-2011_05
Patent number
US07947738B2

Reaction notes

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