Ethyl Acetate → HCID 66725157, compound

HRID 1799195Notes

Reaction equation

HRID 1799195 reaction equation
I([O-])(=O)(=O)=[O:2].[Na+].[C:7]([O:10]CC)(=[O:9])[CH3:8].[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C@@H:20]2[CH2:24][NH:23]C(=O)C2)=[C:16]([CH:26]=C)[CH:15]=1.[BH4-].[Na+]>O.C(#N)C>[ClH:13].[NH2:23][CH2:24][C@@H:20]([C:17]1[CH:18]=[CH:19][C:14]([Cl:13])=[CH:15][C:16]=1[CH2:26][OH:2])[CH2:8][C:7]([OH:10])=[O:9]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 4311764Sodium borohydrideHCID 23667635Sodium periodateHCID 66724999HCID 66724999, compound

Product 1

HCID 66725157HCID 66725157, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

To a cooled (0° C.) solution of sodium periodate (607 mg, 2.85 mmol) in water (3.8 mL) was added a catalytic amount of RuCl3(III) (27 mg, 0.13 mmol) followed by ethyl acetate (10 mL) and acetonitrile (10 mL). The reaction mixture was stirred for 5 min at 0° C. before (4R)-4-(4-chloro-2-vinylphenyl)pyrrolidin-2-one prepared as described above was added. After stirring for an additional two minutes, the reaction mixture was quenched with a Na2S2O3 aq. solution (2 M, 10 mL). The layers were separated and the aqueous phase was extracted with ethyl acetated (4×20 mL). The combined organic phases were dried over MgSO4 and concentrated in vacuo. The resulting crude (2-((3S)-5-oxopyrrolidin-3-yl)-5-chlorobenzaldehyde was dissolved in tetrahydrofuran/water (v/v 1:1, 4.5 mL) and sodium borohydride (70 mg, 1.85 mmol) was added. The mixture was stirred for 20 min at room temperature and then diluted with water (7 mL), extracted with dichloromethane (4×30 mL). The combined organic phases were dried over sodium sulfate and concentrated in vacuo. The crude residue was then treated with a 6N HCl aqueous solution (1.5 mL) and heated overnight at 90° C. The final product was purified by HPLC to provide the title compound. 1H-NMR (400 MHz, CD3OD): δ 2.84-2.70 (m, 2H), 3.08-3.14 (m, 1H), 3.75-3.83 (m, 1H), 4.85 (s, 1H), 4.57-4.60 (d, J=12.0 Hz, 1H), 7.33-7.42 (m, 3H); MS (ESI) m/z 244.06 (M+H)+.

Workup

  1. customprepared
  2. additionabove was added
  3. customthe reaction mixture was quenched with a Na2S2O3 aq. solution (2 M, 10 mL)
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with ethyl
  6. dry with materialThe combined organic phases were dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. dissolutionThe resulting crude (2-((3S)-5-oxopyrrolidin-3-yl)-5-chlorobenzaldehyde was dissolved in tetrahydrofuran/water (v/v 1:1, 4.5 mL)
  9. stirringThe mixture was stirred for 20 min at room temperature
  10. extractionextracted with dichloromethane (4×30 mL)
  11. dry with materialThe combined organic phases were dried over sodium sulfate
  12. concentrationconcentrated in vacuo
  13. additionThe crude residue was then treated with a 6N HCl aqueous solution (1.5 mL)
  14. customThe final product was purified by HPLC

Sources & evidence

ORD record
ord-64390b3a895e4931ac28dd21a902bb02
Source dataset
uspto-grants-2013_01
Patent number
US08344028B2

Reaction notes

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