Cesium carbonate → (2-Bromo-6-{4,4-dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}-4-fluorophenyl)methyl Acetate

HRID 1024058Notes

Reaction equation

HRID 1024058 reaction equation
[CH3:1][C:2]1([CH3:15])[CH2:14][C:5]2[C:6]3[CH2:11][CH2:10][NH:9][C:8](=[O:12])[C:7]=3[S:13][C:4]=2[CH2:3]1.[C:16]([O:19][CH2:20][C:21]1[C:26]([Br:27])=[CH:25][C:24]([F:28])=[CH:23][C:22]=1Br)(=[O:18])[CH3:17].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>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]>[C:16]([O:19][CH2:20][C:21]1[C:22]([N:9]2[CH2:10][CH2:11][C:6]3[C:5]4[CH2:14][C:2]([CH3:15])([CH3:1])[CH2:3][C:4]=4[S:13][C:7]=3[C:8]2=[O:12])=[CH:23][C:24]([F:28])=[CH:25][C:26]=1[Br:27])(=[O:18])[CH3:17]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 580438956,6-Dimethyl-2,3,4,5,6,7-hexahydro-1H-cyclopenta[4,5]thieno[2,3-c]pyridin-1-oneHCID 670165932,6-Dibromo-4-fluorobenzyl acetate

Product 1

HCID 58044256(2-Bromo-6-{4,4-dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}-4-fluorophenyl)methyl AcetateYield 71.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 113h (2 g, 9.05 mmol), 2,6-dibromo-4-fluorobenzyl acetate (101j)(8.8 g, 27.15 mmol), XantPhos (524 mg, 0.9 mmol), Pd2(dba)3 (828 mg, 0.9 mmol) and Cs2CO3 (5.9 g, 18 mmol) in dioxane (200 mL) was heated at 100° C. for 15 h under nitrogen. The reaction mixture was filtered and the filtrated was evaporated in vacuo. The residue was purified by silical-gel column eluting with 1:1 ethyl acetate/petroleum ether to give 113i as a yellow solid (3 g, 71%). MS: (M+H)+ 466.

Workup

  1. filtrationThe reaction mixture was filtered
  2. customthe filtrated was evaporated in vacuo
  3. customThe residue was purified by silical-gel column
  4. washeluting with 1:1 ethyl acetate/petroleum ether

Sources & evidence

ORD record
ord-9495e1aa2a6a4d7092030ca832ee317e
Source dataset
uspto-grants-2014_05
Patent number
US08722676B2

Reaction notes

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