Sodium borohydride → (3-(Pyrid-3-yl)-5-oxo-pyrrolidin-3-yl)acetic acid ethyl ester

HRID 323333Notes

Reaction equation

HRID 323333 reaction equation
[CH2:1]([O:3][C:4](=[O:21])[CH2:5][C:6]([C:19]#[N:20])([C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)[CH2:7][C:8](OCC)=[O:9])[CH3:2].[BH4-].[Na+].ClCCl.CO>CO.O.O.O.O.O.O.[Co](Cl)Cl>[CH2:1]([O:3][C:4](=[O:21])[CH2:5][C:6]1([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[CH2:7][C:8](=[O:9])[NH:20][CH2:19]1)[CH3:2]

Participants

6

Reactant 3

HCID 4311764Sodium borohydrideHCID 21226129Dichloromethane methanolHCID 541828903-cyano-3-(pyrid-3-yl)pentanedioic Acid Diethyl Ester

Product 1

HCID 22009411(3-(Pyrid-3-yl)-5-oxo-pyrrolidin-3-yl)acetic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 517166Dichlorocobalt hexahydrateCatalystHCID 887MethanolSolvent

Procedure

Combine 3-cyano-3-(pyrid-3-yl)pentanedioic acid diethyl ester (50 g, 172 mmol) and cobalt(II)chloride hexahydrate (81.8 g, 344 mmol) in methanol (500 mL). While maintaining the temperature at or below 20° C. with an ice-bath, add portionwise sodium borohydride (65.1 g, 1.72 mol). After the addition is complete, allow the reaction mixture to stand at ambient temperature. After 18 hours, evaporate the reaction mixture in vacuo to obtain a residue. Quench the reaction mixture by adding ammonium chloride and 0.5 M aqueous sodium hydroxide solution. Adjust the pH of the quenched reaction mixture to about 8 using 1 M aqueous hydrochloric acid solution. Filter through celite and extract the aqueous filtrate twice with dichloromethane. Combine the organic layers, dry over Na2SO4, filter, and concentrate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with dichloromethane/methanol 10/1 to give the title compound.

Workup

  1. temperatureWhile maintaining the temperature at or below 20° C. with an ice-bath
  2. additionAfter the addition
  3. customto stand at ambient temperature
  4. customevaporate the reaction mixture in vacuo
  5. customto obtain a residue
  6. customQuench the reaction mixture
  7. additionby adding ammonium chloride and 0.5 M aqueous sodium hydroxide solution
  8. customthe pH of the quenched reaction mixture to about 8 using 1 M aqueous hydrochloric acid solution
  9. filtrationFilter through celite
  10. extractionextract the aqueous filtrate twice with dichloromethane
  11. dry with materialdry over Na2SO4
  12. filtrationfilter
  13. concentrationconcentrate in vacuo
  14. customto give a residue

Sources & evidence

ORD record
ord-04ef77d8212345dbbfa5064ff0ab3354
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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