Acetic Acid → 4-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-1-(4-piperidin-1-yl-butyl)-piperazin-2-one

HRID 559355

Reaction equation

HRID 559355 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:7][C:8]1[CH:9]=[C:10](/[CH:15]=[CH:16]/[C:17]([N:19]2[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][CH2:27][C:28]([N:30](OC)[CH3:31])=O)[C:21](=[O:34])[CH2:20]2)=[O:18])[CH:11]=[CH:12][C:13]=1[Cl:14].CC(C)=O.C(OC(N1CCN(CCC=O)C(=O)C1)=O)(C)(C)C.N1C[CH2:61][CH2:60][CH2:59][CH2:58]1.B.N1C=CC=CC=1.C(O)(=O)C>ClCCCl.C(O)C>[Cl:7][C:8]1[CH:9]=[C:10](/[CH:15]=[CH:16]/[C:17]([N:19]2[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][CH2:27][CH2:28][N:30]3[CH2:31][CH2:61][CH2:60][CH2:59][CH2:58]3)[C:21](=[O:34])[CH2:20]2)=[O:18])[CH:11]=[CH:12][C:13]=1[Cl:14]

Participants

10

Reactant 7

HCID 176Acetic AcidHCID 180AcetoneHCID 8082PiperidineHCID 2723995Borane;pyridineHCID 21226445Aluminium lithium hydrideHCID 57445034Tert-butyl 3-oxo-4-(3-oxopropyl)piperazine-1-carboxylateHCID 866263214-{4-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-2-oxo-piperazin-1-yl}-N-methoxy-N-methyl-butyramide2×

Product 1

HCID 575503994-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-1-(4-piperidin-1-yl-butyl)-piperazin-2-oneYield 53.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 702EthanolSolvent

Conditions

Temperature
-75 °C

Procedure

Lithium aluminum hydride solution (1 M in tetrahydrofuran, 0.13 ml, 0.13 mmol) was added dropwise at −30° C. to a solution of 4-{4-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-2-oxo-piperazin-1-yl}-N-methoxy-N-methyl-butyramide (intermediate 5; 54 mg, 0.13 mmol), then after 10 min the reaction mixture was, cooled to −75° C. and acetone (161 mg, 2.8 mmol) was added. The homogeneous solution was allowed to reach room temperature over 16 h, then partitioned between water and ethyl acetate. The organic layer was washed with brine, dried (MgSO4), and evaporated. The crude aldehyde intermediate (4-{4-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-2-oxo-piperazin-1-yl}-butyraldehyde) and piperidine (10 mg, 0.12 mmol) were dissolved in 1,2-dichloroethane, then a freshly prepared solution of pyridine borane complex (8 M in pyridine, 30 μl, 0.33 mmol) and acetic acid (22 mg, 0.37 mmol) in ethanol (1 ml) was added dropwise at room temperature. The reaction mixture was stirred overnight, then volatile material was removed by rotary evaporation. The residue was purified by chromatography (SiO2; CH2Cl2/MeOH/NH4OH 90:10:0.25) to afford the title compound (28 mg, 51%). Light yellow gum, MS (ISP)=438.2 (M+H)+.

Workup

  1. waitto reach room temperature over 16 h
  2. custompartitioned between water and ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customvolatile material was removed by rotary evaporation
  7. customThe residue was purified by chromatography (SiO2; CH2Cl2/MeOH/NH4OH 90:10:0.25)

Sources & evidence

ORD record
ord-476dd04fd0c94bf29941af7916c4fc23
Source dataset
uspto-grants-2011_11
Patent number
US08063042B2

Linked notes

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