Trifluoroacetic acid → [(1S,6R)-7-Oxo-8-[(1R)-1-phenylethyl]-8-azabicyclo[4.3.0]non-3-en-1-yl]carboxylic acid

HRID 1917380Notes

Reaction equation

HRID 1917380 reaction equation
FC(F)(F)C(O)=O.C([O:12][C:13]([C@:15]12[CH2:23][N:22]([C@@H:24]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH3:25])[C:21](=[O:32])[C@@H:20]1[CH2:19][CH:18]=[CH:17][CH2:16]2)=[O:14])(C)(C)C>ClCCl>[O:32]=[C:21]1[N:22]([C@@H:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH3:25])[CH2:23][C@@:15]2([C:13]([OH:14])=[O:12])[C@H:20]1[CH2:19][CH:18]=[CH:17][CH2:16]2

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67490838[(1S,6R)-7-Oxo-8-[(1R)-1-phenylethyl]-8-azabicyclo[4.3.0]non-3-en-1-yl]carboxylic acid tert-butyl ester

Product 1

HCID 67490831[(1S,6R)-7-Oxo-8-[(1R)-1-phenylethyl]-8-azabicyclo[4.3.0]non-3-en-1-yl]carboxylic acidYield 81.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (18.0 mL) was added to a solution of [(1S,6R)-7-oxo-8-[(1R)-1-phenylethyl]-8-azabicyclo[4.3.0]non-3-en-1-yl]carboxylic acid tert-butyl ester (2.04 g, 5.99 mmol) in dichloromethane (18.0 mL) with stirring under ice-cooling, and the mixture was stirred at room temperature for 1.5 hours. The reaction solution was concentrated under reduced pressure, and trifluoroacetic acid was azeotropically distilled with toluene (×3). A 1 mol/L sodium hydroxide solution (15.0 mL) was added to the resulting residue under ice-cooling, and the mixture was washed with diethyl ether (40 mL×2). The aqueous layer was made acidic with 1 mol/L hydrochloric acid (20 mL) under ice-cooling. Then, the precipitated crystals were collected by filtration and washed with 0.5 mol/L hydrochloric acid, ethyl acetate, and diethyl ether. The resulting crystals were dried under reduced pressure at 50° C. overnight to give 1.40 g of the title compound as white crystals. The aqueous layer of the filtrate was extracted with ethyl acetate (50 mL). The organic layers were combined, washed with water (150 mL) and brine (150 mL), and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to give 250 mg of the title compound as white crystals.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at room temperature for 1.5 hours
  3. concentrationThe reaction solution was concentrated under reduced pressure, and trifluoroacetic acid
  4. distillationwas azeotropically distilled with toluene (×3)
  5. additionA 1 mol/L sodium hydroxide solution (15.0 mL) was added to the resulting residue under ice-
  6. temperaturecooling
  7. washthe mixture was washed with diethyl ether (40 mL×2)
  8. temperaturecooling
  9. filtrationThen, the precipitated crystals were collected by filtration
  10. washwashed with 0.5 mol/L hydrochloric acid, ethyl acetate, and diethyl ether
  11. customThe resulting crystals were dried under reduced pressure at 50° C. overnight

Sources & evidence

ORD record
ord-7231cc44600546a298114339e7ed14d4
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

Loading…