Sodium hydride → 4-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-3-methyl-1-(3-piperidin-1-yl-propyl)-piperazin-2-one

HRID 559354Notes

Reaction equation

[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6](/[CH:11]=[CH:12]/[C:13]([N:15]2[CH2:20][CH2:19][NH:18][C:17](=[O:21])[CH:16]2[CH3:22])=[O:14])[CH:7]=[CH:8][C:9]=1[Cl:10].[Cl:23][CH2:24][CH2:25][CH2:26][N:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>CN(C)C(=O)C.C1(C)C=CC=CC=1>[CH2:9]([Cl:10])[Cl:23].[CH3:13][OH:14].[NH4+:15].[OH-:14].[Cl:3][C:4]1[CH:5]=[C:6](/[CH:11]=[CH:12]/[C:13]([N:15]2[CH2:20][CH2:19][N:18]([CH2:24][CH2:25][CH2:26][N:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)[C:17](=[O:21])[CH:16]2[CH3:22])=[O:14])[CH:7]=[CH:8][C:9]=1[Cl:10]

Participants

Conditions

Temperature: 50 °C

Procedure

Sodium hydride (55% dispersion in mineral oil, 21 mg, 0.48 mmol) was added at room temperature to a solution of 4-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-3-methyl-piperazin-2-one (intermediate 1; 100 mg, 0.32 mmol) in N,N-dimethylacetamide (2 ml), then after 20 min a solution of 1-(3-chloropropyl)-piperidine (prepared from the commercially available hydrochloride salt (127 mg, 0.64 mmol) by basic extraction as described in intermediate 6) in toluene (1 ml) was added. The reaction mixture was stirred for 16 h at 50° C., then partitioned between water and ethyl acetate. The organic layer was washed with brine, dried (MgSO4), and evaporated. Chromatography (SiO2; CH2Cl2/MeOH/NH4OH 95:5:0.25) afforded the title compound (66 mg, 47%). Colorless gum, MS (ISP)=438.4 (M+H)+.

Workup

additionwas added
custompartitioned between water and ethyl acetate
washThe organic layer was washed with brine
dry with materialdried (MgSO4)
customevaporated

Sources & evidence

ORD record: ord-c5d983ccb3404383a6a857c9d146e19c
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063042B2

Reaction notes

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