Sodium Hydroxide → 1-(4-Chloro-phenyl)-4-{3-[7-(1-hydroxy-1-methyl-ethyl)-11H-10-oxa-1-aza-dibenzo[a,d]cyclohepten-5-ylidene]-propyl}-piperazine-2-carboxylic acid amide

HRID 457175Notes

Reaction equation

HRID 457175 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH:16]=[C:17]3[C:23]4[CH:24]=[CH:25][CH:26]=[N:27][C:22]=4[CH2:21][O:20][C:19]4[CH:28]=[CH:29][C:30]([C:32]([OH:35])([CH3:34])[CH3:33])=[CH:31][C:18]3=4)[CH2:10][CH:9]2[C:36]#[N:37])=[CH:4][CH:3]=1.[OH-:38].[Na+]>CO.C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH:16]=[C:17]3[C:23]4[CH:24]=[CH:25][CH:26]=[N:27][C:22]=4[CH2:21][O:20][C:19]4[CH:28]=[CH:29][C:30]([C:32]([OH:35])([CH3:34])[CH3:33])=[CH:31][C:18]3=4)[CH2:10][CH:9]2[C:36]([NH2:37])=[O:38])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 667585841-(4-chloro-phenyl)-4-{3-[7-(1-hydroxy-1-methyl-ethyl)-11H-10-oxa-1-aza-dibenzo[a,d]cyclohepten-5-ylidene]-propyl}-piperazine-2-carbonitrile

Product 1

HCID 667580131-(4-Chloro-phenyl)-4-{3-[7-(1-hydroxy-1-methyl-ethyl)-11H-10-oxa-1-aza-dibenzo[a,d]cyclohepten-5-ylidene]-propyl}-piperazine-2-carboxylic acid amide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1-(4-chloro-phenyl)-4-{3-[7-(1-hydroxy-1-methyl-ethyl)-11H-10-oxa-1-aza-dibenzo[a,d]cyclohepten-5-ylidene]-propyl}-piperazine-2-carbonitrile (0.12 g, 0.23 mmol) in methanol (0.5 mL) and THF (0.5 mL) was added 1.0 N NaOH (0.5 mL, 0.5 mmol) and the resulting mixture was heated to reflux at 80° C. for 18 h. Additional 2.0 N NaOH (0.5 mL, 0.5 mmol) was added to the reaction mixture and refluxed further for 18 h. The reaction mixture was concentrated, acidified to pH 5.0 using 1.0 N HCl and extracted with ethyl acetate (3×). The combined organics were dried over sodium sulfate and concentrated. The crude product was purified on a short plug of silica gel using gradient elution from ethyl acetate/methanol (2–10%) to give the title compound.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperaturerefluxed further for 18 h
  3. concentrationThe reaction mixture was concentrated
  4. extractionextracted with ethyl acetate (3×)
  5. dry with materialThe combined organics were dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe crude product was purified on a short plug of silica gel using gradient elution from ethyl acetate/methanol (2–10%)

Sources & evidence

ORD record
ord-fd79c0b4c58f40e891d6c6fd37896e39
Source dataset
uspto-grants-2007_03
Patent number
US07186729B2

Reaction notes

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