p-Toluenesulfonic acid → HCID 69072799, compound

HRID 1182596Notes

Reaction equation

HRID 1182596 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:14]=[C:15]1O[C:17](=[O:18])[CH2:16]1.C(N(CC)CC)C.[Cl:27][C:28]1[CH:29]=[C:30]([CH:33]=[CH:34][CH:35]=1)[CH:31]=O.N1CCCCC1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[C:53]([CH2:55][CH2:56][O:57][C:58](=[O:63])/[CH:59]=[C:60](\[NH2:62])/[CH3:61])#[N:54]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:17]([C:16]2[CH:31]([C:30]3[CH:33]=[CH:34][CH:35]=[C:28]([Cl:27])[CH:29]=3)[C:59]([C:58]([O:57][CH2:56][CH2:55][C:53]#[N:54])=[O:63])=[C:60]([CH3:61])[NH:62][C:15]=2[CH3:14])=[O:18])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

10

Reactant 7

HCID 6101p-Toluenesulfonic acidHCID 8082PiperidineHCID 8471TriethylamineHCID 114773-ChlorobenzaldehydeHCID 12661DiketeneHCID 143452tert-Butyl piperazine-1-carboxylateHCID 136714102-Cyanoethyl 3-aminocrotonate

Product 1

HCID 69072799HCID 69072799, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

1.48 g (7.97 mmol) of 1-(t-butoxycarbonyl) piperazine, 0.74 ml (9.59 mmol) of diketene and 0.22 ml (1.58 mmol) of triethylamine were stirred in 50 ml of toluene at 80° C. for 5 hours. After ethyl acetate was added, the reaction mixture was washed with saturated aqueous sodium hydrogencarbonate solution. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The obtained substance was dissolved in 50 ml of benzene. 0.94 ml (8.30 mmol) of 3-chlorobenzaldehyde, 0.08 ml of piperidine and catalytic amount of p-toluenesulfonic acid were added and stirred removing water at 120° C. for 7 hours. After adding ethyl acetate, the reaction mixture was washed with 1 N hydrochloric acid and saturated aqueous sodium hydrogencarbonate solution. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by the silica gel chromatography (hexane/ethyl acetate=3/1). The obtained substance was dissolved in 50 ml of 2-propanol. 929 mg (6.03 mmol) of 3-aminocrotonate (2-cyanoethyl) ester was added and stirred at 80° C. for four nights and then, after the solvent was removed, stirred at 120° C. for 4 hours. The reaction mixture was purified by the silica gel chromatography (chloroform/methanol=100/1) to obtain the title compound.

Workup

  1. washthe reaction mixture was washed with saturated aqueous sodium hydrogencarbonate solution
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe obtained substance was dissolved in 50 ml of benzene
  5. customremoving water at 120° C. for 7 hours
  6. additionAfter adding ethyl acetate
  7. washthe reaction mixture was washed with 1 N hydrochloric acid and saturated aqueous sodium hydrogencarbonate solution
  8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by the silica gel chromatography (hexane/ethyl acetate=3/1)
  11. dissolutionThe obtained substance was dissolved in 50 ml of 2-propanol
  12. stirringstirred at 80° C. for four nights
  13. customafter the solvent was removed
  14. stirringstirred at 120° C. for 4 hours
  15. customThe reaction mixture was purified by the silica gel chromatography (chloroform/methanol=100/1)

Sources & evidence

ORD record
ord-c724d85241054658bb856318505341b1
Source dataset
uspto-grants-2007_10
Patent number
US07288544B2

Reaction notes

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