9-Methyl-3,9-diazabicyclo[3.3.1]nonane → 3-(6-Methoxy-naphthalen-2-yl)-9-methyl-3,9-diaza-bicyclo[3.3.1]nonane Fumaric Acid Salt

HRID 643278Notes

Reaction equation

HRID 643278 reaction equation
[CH3:1][N:2]1[CH:7]2[CH2:8][CH2:9][CH2:10][CH:3]1[CH2:4][NH:5][CH2:6]2.Br[C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:22][CH3:23])[CH:18]=2)[CH:13]=1.CC(C)([O-])C.[K+].[C:30]([OH:37])(=[O:36])/[CH:31]=[CH:32]/[C:33]([OH:35])=[O:34]>C(OCC)C.C(O)C.O.O1CCOCC1>[C:30]([OH:37])(=[O:36])/[CH:31]=[CH:32]/[C:33]([OH:35])=[O:34].[CH3:23][O:22][C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][CH:16]=1)[CH:13]=[C:12]([N:5]1[CH2:4][CH:3]3[N:2]([CH3:1])[CH:7]([CH2:8][CH2:9][CH2:10]3)[CH2:6]1)[CH:21]=[CH:20]2

Participants

9

Reactant 4

HCID 189119-Methyl-3,9-diazabicyclo[3.3.1]nonaneHCID 787862-Bromo-6-methoxynaphthaleneHCID 444972Fumaric AcidHCID 23665647Potassium tert-butoxide

Product 1

HCID 1317280613-(6-Methoxy-naphthalen-2-yl)-9-methyl-3,9-diaza-bicyclo[3.3.1]nonane Fumaric Acid Salt

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 9-methyl-3,9-diaza-bicyclo[3.3.1]nonane (2.0 g, 14.3 mmol), 2-bromo-6-methoxynaphthalene (5.07 g, 21.4 mmol), palladacycle (100 mg, 0.11 mmol), potassium tert-butoxide (3.2 g, 28.5 mmol) and dioxane (30 ml) was stirred at reflux for 40 h. The mixture was cooled to room temperature. Water (50 ml) was added and the mixture was extracted with ethylacetate (3×30 ml). The crude product was purified by silica gel column chromatography using a solvent mixture of dichloromethane, methanol and aqueous ammonia (18:1:1%). The fumarate salt was precipitated from 1.1 eq of fumaric acid and a mixture of ethanol and diethylether (2:5). Yield 1.4 g (33%). Mp 190.0-198.3° C. LC-ESI-HRMS of [M+H]+ shows 297.1955 Da. Calc. 297.196688 Da, dev. −4 ppm.

Workup

  1. temperatureat reflux for 40 h
  2. extractionthe mixture was extracted with ethylacetate (3×30 ml)
  3. customThe crude product was purified by silica gel column chromatography
  4. additiona solvent mixture of dichloromethane, methanol and aqueous ammonia (18:1:1%)

Sources & evidence

ORD record
ord-8c412243d5b846edabf952c6726e974f
Source dataset
uspto-grants-2010_04
Patent number
US07700596B2

Reaction notes

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