Water → 2,2,2-Trifluoro-1-[3-(5-methoxy-3-pyridin-3-yl-9H-xanthen-9-yl)-8-aza-bicyclo[3.2.1]oct-8-yl]-ethanone

HRID 733415Notes

Reaction equation

HRID 733415 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[CH:6]([CH:18]3[CH2:24][CH:23]4[N:25]([C:26](=[O:31])[C:27]([F:30])([F:29])[F:28])[CH:20]([CH2:21][CH2:22]4)[CH2:19]3)[C:7]3[C:12]([O:13][C:14]=2[CH:15]=1)=[C:11]([O:16][CH3:17])[CH:10]=[CH:9][CH:8]=3.[N:32]1[CH:37]=[CH:36][CH:35]=[C:34](B(O)O)[CH:33]=1.C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1.[Pd](Cl)Cl.C(PC(C)(C)C)(C)(C)C.C(OCC)(=O)C>[F:28][C:27]([F:29])([F:30])[C:26]([N:25]1[CH:20]2[CH2:21][CH2:22][CH:23]1[CH2:24][CH:18]([CH:6]1[C:5]3[CH:4]=[CH:3][C:2]([C:34]4[CH:33]=[N:32][CH:37]=[CH:36][CH:35]=4)=[CH:15][C:14]=3[O:13][C:12]3[C:7]1=[CH:8][CH:9]=[CH:10][C:11]=3[O:16][CH3:17])[CH2:19]2)=[O:31]

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 578392431-[3-(3-Bromo-5-methoxy-9H-xanthen-9-yl)-8-aza-bicyclo[3.2.1]oct-8-yl]-2,2,2-trifluoro-ethanone2×

Product 1

HCID 578392272,2,2-Trifluoro-1-[3-(5-methoxy-3-pyridin-3-yl-9H-xanthen-9-yl)-8-aza-bicyclo[3.2.1]oct-8-yl]-ethanoneYield 93%

Reagents, catalysts & solvents 3

HCID 86605581di-tert-butylphosphine palladium (II) dichlorideCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 1-[3-(3-bromo-5-methoxy-9H-xanthen-9-yl)-8-aza-bicyclo[3.2.1]oct-8-yl]-2,2,2-trifluoro-ethanone, 5k (0.505 g, 1.02 mmol) in dioxane (15 mL) were added 3-pyridylboronic acid (0.188 g, 1.53 mmol), di-tert-butylphosphine palladium (II) dichloride (35 mg), and a 2 M sodium carbonate solution (1.3 mL, 2.54 mmol), and the mixture was heated at 75° C. for 2 h under an argon atmosphere. The mixture was allowed to cool to rt and water and ethyl acetate were added. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by flash column chromatography (eluent gradient: 50% to 95% EtOAc in heptane) to yield 0.47 g (93%) of title compound 2,2,2-trifluoro-1-[3-(5-methoxy-3-pyridin-3-yl-9H-xanthen-9-yl)-8-aza-bicyclo[3.2.1]oct-8-yl]-ethanone, 6k. MS m/z (MH+) 495.1.

Workup

  1. washThe organic phase was washed with brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography (eluent gradient: 50% to 95% EtOAc in heptane)

Sources & evidence

ORD record
ord-eae0f85871e74f45bc94dec936af6a4e
Source dataset
uspto-grants-2009_09
Patent number
US07589104B2

Reaction notes

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