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

HRID 559359

Reaction equation

HRID 559359 reaction equation
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]

Participants

12

Reactant 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

Product 1

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

Reagents, catalysts & solvents 4

HCID 30318Osmium TetroxideCatalystHCID 111,2-DichloroethaneSolventHCID 702EthanolSolventHCID 18366337Propan-2-one--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

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)+.

Workup

  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)

Sources & evidence

ORD record
ord-4a2f1bcaef924f159a2086988fb27dc5
Source dataset
uspto-grants-2011_11
Patent number
US08063042B2

Linked notes

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