Sodium borohydride → (3-(3,4-Dimethoxyphenyl)-5-oxopyrrolidin-3-yl)acetic acid ethyl ester

HRID 399976Notes

Reaction equation

HRID 399976 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]([C:23]#[N:24])([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=1)[CH2:7][C:8](OCC)=[O:9])[CH3:2].[BH4-].[Na+]>O.O.O.O.O.O.[Co](Cl)Cl.CO>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=2)[CH2:7][C:8](=[O:9])[NH:24][CH2:23]1)[CH3:2]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 153920193-Cyano-3-(3,4-dimethoxyphenyl)pentanedioic diethyl ester

Product 1

HCID 15392020(3-(3,4-Dimethoxyphenyl)-5-oxopyrrolidin-3-yl)acetic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 517166Dichlorocobalt hexahydrateCatalystHCID 887MethanolSolvent

Procedure

Combined 3-cyano-3-(3,4-dimethoxy-phenyl)-pentanedioic acid diethyl ester (16.8 g, 48.0 mmol), methanol (300 mL) and cobalt (II) chloride hexahydrate (22.8 g, 96.0 mmol). Cooled until the internal temperature reached 10° C. Added portionwise so as to maintain the reaction temperature below 20° C., sodium borohydride (44.2 g, 1.17 mol). After addition was complete, the reaction mixture was allowed to warm to ambient temperature and stirred over the weekend. Concentrated in vacuo to obtain a residue. Partitioned between 1N HCl (800 mL) and dichloromethane (800 mL). The organic layer was extracted with 1N HCl (2×200 mL). The combined aqueous layers were extracted with dichloromethane (3×100 mL). The organic layers were combined, dried over Na2 SO4, filtered, and concentrated in vacuo to obtain a residue. The residue was chromatographed on silica gel eluting with ethyl acetate/methanol (20:1) to obtain the title compound: Rf =0.27 (silica gel, 20:1 ethyl acetate/methanol), mp=116°-118° C. Analysis: calculated for C16H21NO5C 62.53; H 6.89; N 4.56; Found C 62.52; H 6.85; N 4.50.

Workup

  1. temperatureCooled until the internal temperature
  2. customreached 10° C
  3. additionAdded portionwise so as
  4. additionAfter addition
  5. concentrationConcentrated in vacuo
  6. customto obtain a residue
  7. customPartitioned between 1N HCl (800 mL) and dichloromethane (800 mL)
  8. extractionThe organic layer was extracted with 1N HCl (2×200 mL)
  9. extractionThe combined aqueous layers were extracted with dichloromethane (3×100 mL)
  10. customdried over Na2 SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customto obtain a residue
  14. customThe residue was chromatographed on silica gel eluting with ethyl acetate/methanol (20:1)

Sources & evidence

ORD record
ord-054623457c2a41e7b958418731395222
Source dataset
uspto-grants-1998_10
Patent number
US05824690

Reaction notes

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