Sodium hydride → (1-(3-carboethoxypropyl)-1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine

HRID 323503Notes

Reaction equation

[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1.[H-].[Na+].Br[CH2:27][CH2:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31]>CN(C)C=O>[C:30]([CH2:29][CH2:28][CH2:27][N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1)([O:32][CH2:33][CH3:34])=[O:31]

Participants

Conditions

Temperature: 80 °C

Procedure

Combine (1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine (0.51 g, 1.61 mmol) and dimethylformamide (15 mL). Add sodium hydride (0.086 g, 60% in oil, 2.15 mmol). Heat to 80° C. After 15 minutes, add ethyl 4-bromobutyrate (0.35 mL, 2.45 mmol) and continue heating at 80° C. After 18 hours, cool and partition the reaction mixture between dichloromethane and a saturated aqueous sodium bicarbonate solution. Separate the layers and extract the organic layer with brine. Dry the organic layer over MgSO4, filter, and concentrate in vacuo to give (1-(3-carboethoxypropyl)-1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine.

Workup

temperaturecontinue heating at 80° C
waitAfter 18 hours
temperaturecool
custompartition the reaction mixture between dichloromethane
customSeparate the layers
extractionextract the organic layer with brine
dry with materialDry the organic layer over MgSO4
filtrationfilter
concentrationconcentrate in vacuo

Sources & evidence

ORD record: ord-ae1d729fb8e946d0a8c5f0d908773ec1
Source dataset: uspto-grants-2001_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06211199B1

Reaction notes

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