Sodium Hydroxide → HCID 68284484, compound

HRID 1527540Notes

Reaction equation

HRID 1527540 reaction equation
C([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]([CH2:15][C:16](=[O:36])[N:17]2[CH2:21][CH2:20][CH2:19][C@H:18]2[C:22](=[O:35])[NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([O:30][C:31]([F:34])([F:33])[F:32])[CH:25]=2)[CH:7]=1)=[O:5])C.[OH-].[Na+]>CO.O>[O:36]=[C:16]([N:17]1[CH2:21][CH2:20][CH2:19][C@H:18]1[C:22](=[O:35])[NH:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([O:30][C:31]([F:34])([F:33])[F:32])[CH:25]=1)[CH2:15][N:8]1[C:9]2[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]([C:4]([OH:5])=[O:3])=[CH:7]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 71009435HCID 71009435, compound

Product 1

HCID 68284484HCID 68284484, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1-{2-oxo-2-[(S)-2-(3-trifluoromethoxy-phenylcarbamoyl)-pyrrolidin-1-yl]ethyl}-1H-indole-3-carboxylic acid ethyl ester (314 mg, 0.62 mmol) in MeOH (12 mL) and water (1.2 mL) was added NaOH 1N (1.87 mL, 1.87 mmol) and the mixture was heated at 80° C. for 6 h. MeOH was concentrated, HCl 1N was added and the residue was extracted with EtOAc. The organic extracts were dried with Na2SO4, filtered and concentrated. The crude residue was purified by preparative HPLC (Interchrom C18-ODB, 10 μm, 28×250 mm, 20% CH3CN in H2O 2.5 min, then 20% to 100% CH3CN in H2O in 32.5 min, CH3CN and H2O containing 0.1% HCOOH; flow: 40 mL/min) to give after lyophilization of the purified fractions the desired compound. TLC, Rf (EtOAc)=0.05; MS (LC/MS): 498.1 [M+Na]+, 474.1 [M−H]−; tR (HPLC conditions a): 3.48 min.

Workup

  1. concentrationMeOH was concentrated
  2. additionHCl 1N was added
  3. extractionthe residue was extracted with EtOAc
  4. dry with materialThe organic extracts were dried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by preparative HPLC (Interchrom C18-ODB, 10 μm, 28×250 mm, 20% CH3CN in H2O 2.5 min
  8. customflow: 40 mL/min) to give after lyophilization of the
  9. custompurified fractions the desired compound
  10. custom3.48 min.

Sources & evidence

ORD record
ord-731ac597567c453a997b223461d867df
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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