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

HRID 323185Notes

Reaction equation

HRID 323185 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+].C(OCC)(=O)C.CO>CO.O.O.O.O.O.O.[Co](Cl)Cl>[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

6

Reactant 3

HCID 4311764Sodium borohydrideHCID 153920193-Cyano-3-(3,4-dimethoxyphenyl)pentanedioic diethyl esterHCID 21584119Ethylacetate methanol

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

Combine 3-cyano-3-(3,4-dimethoxyphenyl)pentanedioic diethyl ester (1.3 g, 3.24 mmol) and cobalt(II)chloride hexahydrate (1.54 g, 6.48 mmol) in methanol (50 mL). While maintaining the temperature at or below 20° C. with an ice-bath, add portionwise sodium borohydride (2.17 g, 57 mmol). After the addition is complete, allow the reaction mixture to stand at ambient temperature for 18 hours. Evaporate the reaction mixture in vacuo to obtain a residue. Partition the residue between dichloromethane and 1M hydrochloric acid solution. Extract the aqueous layer several times with dichloromethane, combine the organic layers, dry over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting with 20/1 ethyl acetate/methanol. Remove residual solvent in vacuo at 82° C. to give the title compound: Rf=0.74 (silica gel, 5/1 ethyl acetate/methanol); mp; 116-118° C. Elemental Analysis calculated for C16H21NO5: C 62.53; H 6.89; N 4.56; Found: C 62.52; H 6.85; N 4.50.

Workup

  1. temperatureWhile maintaining the temperature at or below 20° C. with an ice-bath
  2. additionAfter the addition
  3. customEvaporate the reaction mixture in vacuo
  4. customto obtain a residue
  5. customPartition the residue between dichloromethane and 1M hydrochloric acid solution
  6. extractionExtract the aqueous layer several times with dichloromethane
  7. dry with materialdry over Na2SO4
  8. filtrationfilter
  9. concentrationconcentrate in vacuo
  10. customto obtain a residue
  11. customRemove residual solvent in vacuo at 82° C.

Sources & evidence

ORD record
ord-562658363d3643cebb35d87422565ff0
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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