Cesium carbonate → Methyl 5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzoate

HRID 555153Notes

Reaction equation

HRID 555153 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[CH:9][C:10]2[O:14][C:13]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)=[C:12]([C:22](=[O:25])[NH:23][CH3:24])[C:11]=2[C:26]=1[F:27])(=O)=O.[CH3:30][O:31][C:32]1[CH:41]=[C:40]([CH3:42])[C:39](B2OC(C)(C)C(C)(C)O2)=[CH:38][C:33]=1[C:34]([O:36][CH3:37])=[O:35].C(=O)([O-])[O-].[Cs+].[Cs+]>O.O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:27][C:26]1[C:11]2[C:12]([C:22](=[O:25])[NH:23][CH3:24])=[C:13]([C:15]3[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=3)[O:14][C:10]=2[CH:9]=[CH:8][C:7]=1[C:39]1[C:40]([CH3:42])=[CH:41][C:32]([O:31][CH3:30])=[C:33]([CH:38]=1)[C:34]([O:36][CH3:37])=[O:35]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 59224652Methyl 2-methoxy-4-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 866408624-Fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl trifluoromethanesulfonate

Product 1

HCID 59275657Methyl 5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzoate

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
95 °C

Procedure

A mixture of the above prepared 4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl trifluoromethanesulfonate (assumed 0.211 mmol), methyl 2-methoxy-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (0.078 g, 0.253 mmol), (Ph3P)4Pd (0.024 g, 0.021 mmol) and cesium carbonate (0.103 g, 0.317 mmol) in a mixture of H2O (0.2 mL)/1,4-dioxane (1 mL) was stirred at 95° C. for 2 hours 30 min. The mixture was left standing at r.t. overnight. The mixture was diluted with 3.5 ml 1,4-dioxane, filtered through a Whatman PVDF 0.45 um disk (with 3×1 ml washing). The filtrate was concentrated. The mixture was added with 3.5 ml 1N HCl, and then 6 ml H2O (yellow solid deposited on the wall of the flask). The aqueous was decanted, and the residue washed with 3×2 ml H2O and dried. LC/MS were performed by using Shimadzu-VP instrument with UV detection at 220 nm and Waters MICROMASS®. HPLC method: Solvent A=10% MeOH-90% H2O-0.1% TFA, Solvent B=90% MeOH-10% H2O-0.1% TFA, Start % B=0, Final % B=100, Gradient time=2 min, Stop time=3 min, Flow Rate=5 ml/min, Column: PHENOMENEX® Luna, 3.0×50 mm, S10; (ES+) m/z (M+H)+=466.27, HPLC Rt=1.708 min.

Workup

  1. additionA mixture of the
  2. waitThe mixture was left
  3. waitstanding at r.t. overnight
  4. filtrationfiltered through a Whatman PVDF 0.45 um disk (with 3×1 ml washing)
  5. concentrationThe filtrate was concentrated
  6. additionThe mixture was added with 3.5 ml 1N HCl
  7. customThe aqueous was decanted
  8. washthe residue washed with 3×2 ml H2O
  9. customdried
  10. customB=100, Gradient time=2 min
  11. customtime=3 min, Flow Rate=5 ml/min, Column

Sources & evidence

ORD record
ord-ad1f5d0939944c7aa11d0279c46f2b25
Source dataset
uspto-grants-2011_11
Patent number
US08048887B2

Reaction notes

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