1,10-Phenanthroline → (R)-3-(5,5-Dioxo-5H-5lambda6-dibenzothiophen-3-yloxy)-1-aza-bicyclo[2.2.2]octane

HRID 902983Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]2[C:9]3[CH:10]=[CH:11][C:12](Br)=[CH:13][C:8]=3[S:7](=[O:16])(=[O:15])[C:6]=2[CH:17]=1.[N:18]12[CH2:25][CH2:24][CH:21]([CH2:22][CH2:23]1)[C@@H:20]([OH:26])[CH2:19]2.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.[Cu]I>[O:15]=[S:7]1(=[O:16])[C:6]2[CH:17]=[CH:2][CH:3]=[CH:4][C:5]=2[C:9]2[CH:10]=[CH:11][C:12]([O:26][C@@H:20]3[CH:21]4[CH2:24][CH2:25][N:18]([CH2:23][CH2:22]4)[CH2:19]3)=[CH:13][C:8]1=2

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 3,7-dibromodibenzothiophene-5,5-dioxide (0.60 g, 1.75 mmol; see J. Med. Chem. 1978, 21, 1084), (R)-(−)-quinuclidin-3-ol (280 mg, 2.2 mmol; Acros), copper(I) iodide (33 mg, 0.17 mmol; Aldrich), 1,10-phenanthroline (63 mg, 0.35 mol; Aldrich) and powdered cesium carbonate (0.86 g, 2.64 mmol; Aldrich) in toluene (2 mL) was heated to 110° C. with vigorous stirring for 30 h. After cooling to room temperature, the reaction mixture was filtered through diatomaceous earth, rinsing with ethyl acetate and dichloromethane, and the residue purified by flash chromatography (80 g silica gel, 1:10:89 NH4OH-MeOH-CH2Cl2) to afford the title compound (0.23 g, 0.67 mmol; 38% yield): MS (DCl/NH3): m/z 342 (M+1)+.

Workup

temperatureAfter cooling to room temperature
filtrationthe reaction mixture was filtered through diatomaceous earth
washrinsing with ethyl acetate and dichloromethane
customthe residue purified by flash chromatography (80 g silica gel, 1:10:89 NH4OH-MeOH-CH2Cl2)

Sources & evidence

ORD record: ord-fe6298a4bdf244cab3c080d60f71ddeb
Source dataset: uspto-grants-2008_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07365193B2

Reaction notes

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