Cesium carbonate → 3-[2-(4-Fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-5-yl]benzoic acid

HRID 1671854Notes

Reaction equation

HRID 1671854 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].FC(F)(F)S(O[C:13]1[CH:14]=[CH:15][C:16]2[O:20][C:19]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[C:18]([C:28](=[O:31])[NH:29][CH3:30])[C:17]=2[CH:32]=1)(=O)=O.B([C:38]1[CH:39]=[C:40]([CH:44]=[CH:45][CH:46]=1)[C:41]([OH:43])=[O:42])(O)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.O>[F:27][C:24]1[CH:25]=[CH:26][C:21]([C:19]2[O:20][C:16]3[CH:15]=[CH:14][C:13]([C:38]4[CH:39]=[C:40]([CH:44]=[CH:45][CH:46]=4)[C:41]([OH:43])=[O:42])=[CH:32][C:17]=3[C:18]=2[C:28](=[O:31])[NH:29][CH3:30])=[CH:22][CH:23]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 27339573-Carboxyphenylboronic acidHCID 59275663(4-Fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl trifluoromethanesulfonate

Product 1

HCID 592754243-[2-(4-Fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-5-yl]benzoic acid

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

Cesium carbonate (3.5 g, 10.7 mmol) was added to Pd(Ph3P)4 (108 mg, 0.093 mmol), 2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl trifluoromethanesulfonate (3.0 g, 7.19 mmol), 3-boronobenzoic acid (1.97 g, 11.86 mmol). Dioxane (60 ml) and water (12 ml) was added at rt. The reaction was degassed 3× and then heated to 95° C. and allowed to stir overnight. It was allowed to cool to rt. The mixture was diluted with EtOAc and washed with 1M HCl, and sat NaCl. The precipitate that formed was filtered and dried overnight at 55° C. under vacuum. The remaining organic phase was concentrated and triturated with DCM, followed by hot DCE and finally hot MeOH to afford the titled compound which was combined with the previously collected precipitate (2.4 g, 87%). LC-MS retention time: 1.19 min; m/z (MH+): 390. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 10u C18 3.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 10% MeOH/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% MeOH/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. customThe reaction was degassed 3×
  2. temperatureto cool to rt
  3. additionThe mixture was diluted with EtOAc
  4. washwashed with 1M HCl
  5. customThe precipitate that formed
  6. filtrationwas filtered
  7. customdried overnight at 55° C. under vacuum
  8. concentrationThe remaining organic phase was concentrated
  9. customtriturated with DCM

Sources & evidence

ORD record
ord-0555fedc0f2a435f8acd0fd640b668c7
Source dataset
uspto-grants-2011_08
Patent number
US07994171B2

Reaction notes

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