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

HRID 559359

Reaktionsgleichung

Reaktionsgleichung von HRID 559359
I([O-])(=O)(=O)=O.[Na+].[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][CH:28]=C)[C:21](=[O:30])[CH:20]2[CH3:31])=[O:18])[CH:11]=[CH:12][C:13]=1[Cl:14].ClC1C=C(/C=C/C(N2C[CH2:48][N:47]([CH2:50][CH2:51][CH2:52][CH:53]=O)C(=O)C2)=O)C=CC=1Cl.N1CCCCC1.B.N1C=CC=CC=1.C(O)(=O)C.[OH-].[NH4+]>CC(C)=O.O.ClCCCl.C(O)C.[Os](=O)(=O)(=O)=O>[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:47]3[CH2:48][CH2:53][CH2:52][CH2:51][CH2:50]3)[C:21](=[O:30])[CH:20]2[CH3:31])=[O:18])[CH:11]=[CH:12][C:13]=1[Cl:14]

Komponenten

12

Edukt 7

HCID 176Acetic AcidHCID 8082PiperidineHCID 14923Ammonium HydroxideHCID 2723995Borane;pyridineHCID 23667635Sodium periodateHCID 669992764-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-3-methyl-1-pent-4-enyl-piperazin-2-one2×HCID 872317494-{4-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-2-oxo-piperazin-1-yl}-butyraldehyde

Produkt 1

HCID 575503914-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-3-methyl-1-(4-piperidin-1-yl-butyl)-piperazin-2-oneAusbeute 11 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 30318Osmium TetroxideKatalysatorHCID 111,2-DichloroethaneLösungsmittelHCID 702EthanolLösungsmittelHCID 18366337Propan-2-one--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Sodium metaperiodate (310 mg, 1.45 mmol) and osmium(VIII) oxide (2.5% solution in tert-butylalcohol, 49 μl, 48 μmol) were added at 0° C. to a solution of 4-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-3-methyl-1-pent-4-enyl-piperazin-2-one (intermediate 20; 184 mg, 0.48 mmol) in acetone/water 1:1 (10 ml). The reaction mixture was stirred at 0° C. for 30 min, then allowed to reach room temperature over 45 min, then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (MgSO4), and evaporated. The crude aldehyde intermediate [4-{-4-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-3-methyl-2-oxo-piperazin-1-yl}-butyraldehyde] and piperidine (33 mg, 0.39 mmol) were dissolved in 1,2-dichloroethane (1.5 ml), then a freshly prepared solution of pyridine borane complex (8 M in pyridine, 71 μl, 0.78 mmol) and acetic acid (69 mg, 1.16 mmol) in ethanol (1.5 ml) was added dropwise at room temperature. The reaction mixture was stirred overnight, then 25%. aq. ammonium hydroxide solution (0.16 ml) was added, and 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 (15 mg, 11%). Light yellow solid, MS (ISP)=452.1 (M+H)+.

Aufarbeitung

  1. waitto reach room temperature over 45 min
  2. custompartitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. stirringThe reaction mixture was stirred overnight
  7. customvolatile material was removed by rotary evaporation
  8. customThe residue was purified by chromatography (SiO2; CH2Cl2/MeOH/NH4OH 90:10:0.25)

Quellen und Nachweise

ORD-Eintrag
ord-4a2f1bcaef924f159a2086988fb27dc5
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08063042B2

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