Sodium Hydroxide → HCID 46220531, compound

HRID 589598Notes

Reaction equation

HRID 589598 reaction equation
C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([S:12](=[O:37])(=[O:36])[N:13]([C:26]2[S:30][C:29]3[CH:31]=[CH:32][CH:33]=[CH:34][C:28]=3[C:27]=2[CH3:35])[CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=2)[CH2:8][CH2:7]1)=[O:5])C.[OH-].[Na+]>CO>[CH3:35][C:27]1[C:28]2[CH:34]=[CH:33][CH:32]=[CH:31][C:29]=2[S:30][C:26]=1[N:13]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]([F:24])([F:23])[F:25])=[CH:17][CH:16]=1)[S:12]([N:9]1[CH2:8][CH2:7][CH:6]([C:4]([OH:5])=[O:3])[CH2:11][CH2:10]1)(=[O:36])=[O:37]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 59376669HCID 59376669, compound

Product 1

HCID 46220531HCID 46220531, compoundYield 43.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of compound 5-A (27 mg, 0.049 mmol), dissolved in MeOH (1.0 mL), was added 3N NaOH (24 μL, 0.073 mmol) and the reaction mixture was refluxed for 18 hours. The reaction was cooled and the solvent evaporated under reduced pressure. The residual solid was partitioned between H2O and EtOAc, the organic layer collected, dried over Na2SO4, filtered and the solvent evaporated under reduced pressure. The crude material was purified by reverse-phase semi-prep HPLC (method 3) eluting with a 50% MeCN—H2O (0.1% TFA) to 70% MeCN—H2O (0.1% TFA) gradient to afford 11.2 mg of compound 10 as a white solid. 1H-NMR (CD3OD, 400 MHz): δ 7.71-7.86 (m, 1H), 7.54-7.61 (m, 1H), 7.29-7.42 (m, 4H), 7.10-7.23 (m, 2H), 4.72-4.85 (br s, 2H), 3.63-3.79 (m, 2H), 2.95-3.11 (m, 2H), 2.44-2.61 (m, 1H), 1.99 (s, 3H), 1.87-1.96 (m, 2H), 1.60-1.81 (m, 2H); MS (method 2): m/z 528.9 (MH+); HPLC (method 1): Rt 6.68 minutes.

Workup

  1. temperaturethe reaction mixture was refluxed for 18 hours
  2. temperatureThe reaction was cooled
  3. customthe solvent evaporated under reduced pressure
  4. customThe residual solid was partitioned between H2O and EtOAc
  5. customthe organic layer collected
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customthe solvent evaporated under reduced pressure
  9. customThe crude material was purified by reverse-phase semi-prep HPLC (method 3)
  10. washeluting with a 50% MeCN—H2O (0.1% TFA) to 70% MeCN—H2O (0.1% TFA) gradient

Sources & evidence

ORD record
ord-99b8024469e7456abfe4c79c085cc4ed
Source dataset
uspto-grants-2016_01
Patent number
US09233947B2

Reaction notes

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