Sodium Iodide → 1-(t-butoxycarbonyl)-4-(1-(2-(trifluoromethoxy)ethyl)-1H-benzimidazol-2-yl)[1,4]diazepane

HRID 2230702Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[NH:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[F:26][C:27]([F:38])([F:37])[O:28]OCCOS(C)(=O)=O.[I-].[Na+].[C:41](OCC)(=O)[CH3:42]>C(OCC)(=O)C.CCCCCC.CCCCCC.CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:16]([CH2:41][CH2:42][O:28][C:27]([F:26])([F:37])[F:38])[C:17]3[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=3[N:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 80 °C

Procedure

Combine 1-(t-butoxycarbonyl)-4-(1H-benzimidazol-2-yl)[1,4]diazepane (0.31 g, 1 mmol) and dimethylformamide (8 mL). Cool in an ice-bath. Add sodium hydride (0.024 g, 1 mmol). After 2 hours, add 2-(methanesulfonyloxy)ethyl trifluoromethoxy ether (0.31 g, 1.5 mmol) and sodium iodide (0.14 g, 1 mmol). Heat to 80° C. After 6 hours, cool to ambient temperature. After 56 hours dilute the reaction mixture with ethyl acetate and extract brine. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting sequentially with hexane, 30% ethyl acetate/hexane and then 50% ethyl acetate/hexane to give 1-(t-butoxycarbonyl)-4-(1-(2-(trifluoromethoxy)ethyl)-1H-benzimidazol-2-yl)[1,4]diazepane; Rf=0.24 (silica gel, 50% ethyl acetate/hexane).

Workup

temperatureCool in an ice-bath
waitAfter 6 hours
temperaturecool to ambient temperature
extractionextract brine
dry with materialDry the organic layer over MgSO4
filtrationfilter
customevaporate in vacuo
customto give a residue

Sources & evidence

ORD record: ord-9e0d7af6430c45d986839a83d987b179
Source dataset: uspto-grants-2002_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06423704B1

Reaction notes

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