Cesium carbonate → HCID 11247685, compound

HRID 1012598Notes

Reaction equation

HRID 1012598 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH3:9].[NH2:10][C:11]1[CH:38]=[CH:37][C:14]([C:15]([C:17]2[CH:18]=[C:19]([CH:33]=[CH:34][C:35]=2[CH3:36])[C:20]([NH:22][CH2:23][CH2:24][O:25][Si](C(C)(C)C)(C)C)=[O:21])=[O:16])=[C:13]([Cl:39])[CH:12]=1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+].O.O.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOC(C)=O.O>[Cl:39][C:13]1[CH:12]=[C:11]([NH:10][C:2]2[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=2[CH3:9])[CH:38]=[CH:37][C:14]=1[C:15]([C:17]1[CH:18]=[C:19]([CH:33]=[CH:34][C:35]=1[CH3:36])[C:20]([NH:22][CH2:23][CH2:24][OH:25])=[O:21])=[O:16]

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 967432-Bromo-5-fluorotolueneHCID 634876Binap, (A+-)-HCID 11726816Tetrabutylammonium Fluoride TrihydrateHCID 67314568HCID 67314568, compound

Product 1

HCID 11247685HCID 11247685, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
100 °C

Procedure

2-Bromo-5-fluorotoluene (8 μL, 0.11 mmol) was dissolved in 1 mL dry 1,4-dioxane in a vial under an argon atmosphere. Compound 430 (42 mg, 0.09 mmol) was added and dissolved in the solvent. Rac-BINAP (2.1 mg, 0.003 mmol), Pd2(dba)3 (2.0 mg, 0.002 mmol) and Cs2CO3 (41 mg, 0.13 mmol) were added, and the reaction mixture was stirred under an argon atmosphere at 100° C. for 72 h. The reaction mixture was filtered and then dissolved in THF (1.00 mL). Tetrabutylammonium fluoride trihydrate (37 mg, 0.12 mmol) was added to the solution and the mixture was stirred at 60° C. for 45 min. The reaction mixture was poured into a mixture of EtOAc/water. The organic phase was washed with Na2CO3 (aq.), water, dried (MgSO4), filtered, and concentrated in vacuo to afford the crude product. The crude product was purified by chromatography eluting EtOAc to afford the title compound as yellow/brown oil. 13C NMR (CDCl3) δ 195.6, 167.8, 160.6, 150.4, 141.2, 140.2, 136.5, 135.7, 134.3, 133.6, 131.5, 131.4, 128.8, 127.4, 127.4, 126.9, 117.8, 115.2, 113.9, 111.7, 77.2, 62.2, 42.9, 20.2, 18.1.

Workup

  1. dissolutiondissolved in the solvent
  2. filtrationThe reaction mixture was filtered
  3. dissolutiondissolved in THF (1.00 mL)
  4. stirringthe mixture was stirred at 60° C. for 45 min
  5. washThe organic phase was washed with Na2CO3 (aq.), water
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford the crude product
  10. customThe crude product was purified by chromatography
  11. washeluting EtOAc

Sources & evidence

ORD record
ord-9924cdab132443acacdd76ead543d7a7
Source dataset
uspto-grants-2011_07
Patent number
US07977387B2

Reaction notes

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