9-Methyl-3,9-diazabicyclo[3.3.1]nonane → 3-(3,4-Dichloro-phenyl)-9-methyl-3,9-diaza-bicyclo[3.3.1]nonane Fumaric Acid Salt

HRID 655345Notes

Reaction equation

HRID 655345 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:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=1.CC(C)([O-])C.[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[C:60]([OH:67])(=[O:66])/[CH:61]=[CH:62]/[C:63]([OH:65])=[O:64]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)C.C(O)C.O.O1CCOCC1>[C:60]([OH:67])(=[O:66])/[CH:61]=[CH:62]/[C:63]([OH:65])=[O:64].[Cl:18][C:15]1[CH:16]=[C:17]([N:5]2[CH2:4][CH:3]3[N:2]([CH3:1])[CH:7]([CH2:8][CH2:9][CH2:10]3)[CH2:6]2)[CH:12]=[CH:13][C:14]=1[Cl:19]

Participants

11

Reactant 5

HCID 189119-Methyl-3,9-diazabicyclo[3.3.1]nonaneHCID 290134-Bromo-1,2-dichlorobenzeneHCID 444972Fumaric AcidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23665647Potassium tert-butoxide

Product 1

HCID 1317280603-(3,4-Dichloro-phenyl)-9-methyl-3,9-diaza-bicyclo[3.3.1]nonane Fumaric Acid Salt

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 9-methyl-3,9-diaza-bicyclo[3.3.1]nonane (0.50 g, 3.56 mmol), 1-bromo-3,4-dichlorobenzene (1.61 g, 7.13 mmol), potassium tert-butoxide (0.80 g, 7.13 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl (0.050 g, 0.105 mmol) and palladium (II) acetate (0.025 g, 0.111 mmol) and dioxane (10 ml) was stirred at 110° C. for 20 min. Water (30 ml) was added followed by extraction with ethylactate (3×10 ml). The organic phase was dried and evaporated. The crude product was purified by silica gel column chromatography using a solvent mixture of dichloromethane, methanol and aqueous ammonia (18-1-1%). The pure product was isolated. Yield 211 mg (20%). The fumarate salt was precipitated from 1.1 eq of fumaric acid and a mixture of ethanol and diethylether (2:5). Mp 187-189° C. LC-ESI-HRMS of [M+H]+ shows 285.092 Da. Calc. 285.092529 Da, dev. −1.9 ppm.

Workup

  1. extractionfollowed by extraction with ethylactate (3×10 ml)
  2. customThe organic phase was dried
  3. customevaporated
  4. customThe crude product was purified by silica gel column chromatography
  5. additiona solvent mixture of dichloromethane, methanol and aqueous ammonia (18-1-1%)
  6. customThe pure product was isolated

Sources & evidence

ORD record
ord-71b8e5e24e874b14a72805c838bff4ff
Source dataset
uspto-grants-2011_12
Patent number
US08071598B2

Reaction notes

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