Carbon Dioxide → 9-Benzyl-3-(4-trifluoromethoxy-phenyl)-3,9-diaza-bicyclo[3.3.1]nonane-2,4-dione

HRID 2110155Notes

Reaction equation

Cl.[CH2:2]([N:9]1[C@H:14]([C:15]([OH:17])=O)[CH2:13][CH2:12][CH2:11][C@@H:10]1[C:18]([OH:20])=O)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[F:21][C:22]([F:32])([F:31])[O:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[CH:26][CH:25]=1.C(=O)=O>O1CCOCC1>[CH2:2]([N:9]1[CH:10]2[CH2:11][CH2:12][CH2:13][CH:14]1[C:15](=[O:17])[N:28]([C:27]1[CH:29]=[CH:30][C:24]([O:23][C:22]([F:21])([F:31])[F:32])=[CH:25][CH:26]=1)[C:18]2=[O:20])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

Conditions

Temperature: 100 °C

Procedure

1,1-Carbonyl diimidazole (CDl; 1.2 g, 7.4 mmol) was added to a mixture of cis-1-benzyl-piperidine-2,6-dicarboxylic acid hydrochloride (1.0 g, 3.34 mmol) and dioxane (10 mL) at rt under N2. The mixture was heated at 100° C. After 15 min, a solution of 4-trifluoromethoxyaniline (600 mg, 3.39 mmol) and dioxane (2 mL) was added. After an additional 2 h, CDl (500 mg, 3.08 mmol) was added (Caution: CO2 evolution). After an additional 1 h, the reaction was allowed to cool to rt, concentrated, diluted with ethyl acetate (120 mL) and washed with 0.5N HCl (100 mL×2). The organic extract was dried, filtered, concentrated, and purified by silica gel chromatography (1:0→4:1; hexanes:ethyl acetate) to give 9-benzyl-3-(4-trifluoromethoxy-phenyl)-3,9-diaza-bicyclo[3.3.1]nonane-2,4-dione: MS (ESI): 405.4 (M+H).

Workup

waitAfter an additional 2 h
waitAfter an additional 1 h
temperatureto cool to rt
concentrationconcentrated
additiondiluted with ethyl acetate (120 mL)
washwashed with 0.5N HCl (100 mL×2)
extractionThe organic extract
customwas dried
filtrationfiltered
concentrationconcentrated
custompurified by silica gel chromatography (1:0→4:1; hexanes:ethyl acetate)

Sources & evidence

ORD record: ord-650c7ead9e754b5f93c19b0caaa30197
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07517884B2

Reaction notes

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