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

HRID 559355

反応式

HRID 559355 の反応式
[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]

参加物

10

反応物 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 回

生成物 1

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

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 702Ethanol溶媒

反応条件

温度
-75 °C

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-476dd04fd0c94bf29941af7916c4fc23
出典データセット
uspto-grants-2011_11
特許番号
US08063042B2

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