Sodium Hydroxide → HCID 66653291, compound

HRID 1524302Notes

Reaction equation

HRID 1524302 reaction equation
C[O:2][C:3](=[O:26])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15](=[O:25])[NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]#[N:24])[CH:18]=2)[CH:5]=1.[OH-].[Na+]>CO>[C:23]([C:19]1[CH:18]=[C:17]([NH:16][C:15]([N:11]2[CH2:12][CH2:13][CH2:14][C@@H:10]2[C:6]2[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=2)[C:3]([OH:26])=[O:2])=[O:25])[CH:22]=[CH:21][CH:20]=1)#[N:24]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 66653264Benzoic acid, 3-[(2R)-1-[[(3-cyanophenyl)amino]carbonyl]-2-pyrrolidinyl]-, methyl ester

Product 1

HCID 66653291HCID 66653291, compoundYield 41.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
5 °C

Procedure

To a stifling solution of 3-[(R)-1-(3-cyano-phenylcarbamoyl)-pyrrolidin-2-yl]-benzoic acid methyl ester (1.086 g, 2.487 mmol) in MeOH (30 mL) at room temperature add 5 M NaOH aqueous solution (10 mL, 49.74 mmol) and stir the reaction at ambient temp for 18 h. Cool the reaction to 0° C. in ice and quench with slow addition of conc. HCl (5 mL) over 15 min, maintaining internal temp at 5° C., to a final pH of 1. Extract the cold suspension with EtOAc (2×100 mL), and wash the organics with water (2×100 mL). Dry the organic layer (Na2SO4), concentrate to a residue in vacuo. Purify this by silica gel chromatography eluting with a gradient of 50% EtOAc/hexane to 100% EtOAc. Pool and concentrate fractions containing product, and triturate the residue in Et2O and hexane to afford 3-[(R)-1-(3-cyano-phenylcarbamoyl)-pyrrolidin-2-yl]-benzoic acid as a solid (347 mg).

Workup

  1. customthe reaction at ambient temp for 18 h
  2. temperatureCool
  3. customthe reaction to 0° C. in ice
  4. customquench with slow addition of conc. HCl (5 mL) over 15 min
  5. extractionExtract the cold suspension with EtOAc (2×100 mL)
  6. washwash the organics with water (2×100 mL)
  7. dry with materialDry the organic layer (Na2SO4)
  8. concentrationconcentrate to a residue in vacuo
  9. customPurify this by silica gel chromatography
  10. washeluting with a gradient of 50% EtOAc/hexane to 100% EtOAc
  11. concentrationPool and concentrate fractions
  12. additioncontaining product
  13. customtriturate the residue in Et2O

Sources & evidence

ORD record
ord-2d277ba678e44c9a8ae706444556d945
Source dataset
uspto-grants-2015_07
Patent number
US09079880B2

Reaction notes

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