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

HRID 553049Notes

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 (DCI/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-23bb82a4d8734297b03143a522c718ca
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07951791B2

Reaction notes

Loading…