Citric Acid → HCID 18510835, compound

HRID 1370549Notes

Reaction equation

HRID 1370549 reaction equation
FC(F)(F)C(O)=O.C(O[C:13]([N:15]1[CH2:20][CH2:19][N:18]([C:21]2[C:29]([Cl:30])=[C:28]3[C:24]([CH2:25][N:26]([CH:32]4[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]4)[C:27]3=[O:31])=[CH:23][CH:22]=2)[CH2:17][CH2:16]1)=O)(C)(C)C.C(=O)([O-])[O-].[K+].[K+].[C:44]1([CH:50]([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[CH2:51]CBr)[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl.CN(C)C=O>[Cl:30][C:29]1[C:21]([N:18]2[CH2:19][CH2:20][N:15]([CH2:13][CH2:51][CH:50]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[CH2:16][CH2:17]2)=[CH:22][CH:23]=[C:24]2[C:28]=1[C:27](=[O:31])[N:26]([CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1)[CH2:25]2

Participants

8

Reactant 5

HCID 311Citric AcidHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 883331,1'-(3-Bromopropylidene)bisbenzeneHCID 18510918HCID 18510918, compound

Product 1

HCID 18510835HCID 18510835, compoundYield 32.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.125 ml) was added at 0° C. to a solution of 6-[4-(t-butoxycarbonyl)piperazin-1-yl]-7-chloro-2-cyclohexyl-2,3-dihydro-1H-isoindol-1-one (43 mg, 0.1 mmol), obtained in Example 45, in dichloromethane (1 ml). The mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated under the reduced pressure. A saturated aqueous NaHCO3 solution was then added thereto. The mixture was extracted with chloroform. The extract was washed with saturated saline, and then dried over anhydrous MgSO4. The solvent was then removed by distillation under the reduced pressure. Potassium carbonate (28 mg, 0.2 mmol) and 3,3-diphenylpropyl bromide (30 mg, 0.11 mmol) were added at 0° C. to a solution of the crude product, thus obtained, in N,N-dimethylformamide (1 ml). The mixture was stirred at 50° C. for 5 hr. The temperature of the system was then returned to room temperature, and a 0.1 N aqueous citric acid solution was added thereto. The mixture was extracted with ethyl acetate, washed with saturated saline, and then dried over anhydrous MgSO4. The solvent was then removed by distillation under the reduced pressure. The residue was purified by preparative TLC (chloroform:methanol=30:1) to give 17 mg (32%) of the title compound.

Workup

  1. concentrationThe reaction solution was concentrated under the reduced pressure
  2. additionA saturated aqueous NaHCO3 solution was then added
  3. extractionThe mixture was extracted with chloroform
  4. washThe extract was washed with saturated saline
  5. dry with materialdried over anhydrous MgSO4
  6. customThe solvent was then removed by distillation under the reduced pressure
  7. stirringThe mixture was stirred at 50° C. for 5 hr
  8. customwas then returned to room temperature
  9. extractionThe mixture was extracted with ethyl acetate
  10. washwashed with saturated saline
  11. dry with materialdried over anhydrous MgSO4
  12. customThe solvent was then removed by distillation under the reduced pressure
  13. customThe residue was purified by preparative TLC (chloroform:methanol=30:1)

Sources & evidence

ORD record
ord-eba48f522bbf41d2afc66ae3c03b7cd8
Source dataset
uspto-grants-2003_06
Patent number
US06583144B2

Reaction notes

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