Cesium carbonate → 9-(8-Aza-bicyclo[3.2.1]oct-3-ylidene)-5-phenyl-9H-xanthene-3-carboxylic acid diethylamide

HRID 425297Notes

Reaction equation

HRID 425297 reaction equation
[CH2:1]([N:3]([CH2:29][CH3:30])[C:4]([C:6]1[CH:7]=[CH:8][C:9]2[C:10](=[C:21]3[CH2:27][CH:26]4[NH:28][CH:23]([CH2:24][CH2:25]4)[CH2:22]3)[C:11]3[C:16]([O:17][C:18]=2[CH:19]=1)=[C:15](Br)[CH:14]=[CH:13][CH:12]=3)=[O:5])[CH3:2].[C:31]1(B(O)O)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:1]([N:3]([CH2:29][CH3:30])[C:4]([C:6]1[CH:7]=[CH:8][C:9]2[C:10](=[C:21]3[CH2:27][CH:26]4[NH:28][CH:23]([CH2:24][CH2:25]4)[CH2:22]3)[C:11]3[C:16]([O:17][C:18]=2[CH:19]=1)=[C:15]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH:14]=[CH:13][CH:12]=3)=[O:5])[CH3:2]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 66827Phenylboronic AcidHCID 469179409-(8-Aza-bicyclo[3.2.1]oct-3-ylidene)-5-bromo-9H-xanthene-3-carboxylic acid diethylamide

Product 1

HCID 469179959-(8-Aza-bicyclo[3.2.1]oct-3-ylidene)-5-phenyl-9H-xanthene-3-carboxylic acid diethylamideYield 90.7%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 9-(8-aza-bicyclo[3.2.1]oct-3-ylidene)-5-bromo-9H-xanthene-3-carboxylic acid diethylamide (0.170, 0.363 mmol), phenylboronic acid (0.049 g, 0.40 mmol) and cesium carbonate (0.236 g, 0.726 mmol) in dioxane (4 mL) and ethanol (1 mL) was treated with dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (13 mg), and the resulting mixture was heated at reflux for 2 h. The reaction mixture was cooled to room temperature, and the inorganics removed by filtration and washed successively with dioxane, ethanol and dichloromethane. The solvents were evaporated in vacuo. The residue was purified by reverse phase (C18) preparative HPLC, using a gradient of acetonitrile (10% to 90%) in water with trifluoroacetate (0.1%) as the eluant to give the title compound (0.153 g) as a colorless solid. MS: m/z 465.3 (MH+). 1H NMR (DMSO-d6): δ 1.05-1.20 (br m, 6H 0, 1.31 d, 2H, J=8.2 Hz), 1.75-1.85 (br m, 2H), 2.90-3.10 (m, 4H), 3.15-3.50 (br m, 4H), 4.03 br s, 2H), 7.10 (d, 1H, J=1.5 Hz), 7.20 (d of d, 1H, J=1.5 & 7.9 Hz), 7.32 (t, 1H, J=7.5 Hz), 7.40-7.63 (m, 8H), 8.83 (br s, 1H 0 and 9.16 (br d, 1H).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureat reflux for 2 h
  3. customthe inorganics removed by filtration
  4. washwashed successively with dioxane, ethanol and dichloromethane
  5. customThe solvents were evaporated in vacuo
  6. customThe residue was purified by reverse phase (C18) preparative HPLC

Sources & evidence

ORD record
ord-f4da97f31b6848069a05dc628bf3d352
Source dataset
uspto-grants-2012_01
Patent number
US08106207B2

Reaction notes

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