Cesium carbonate → 3-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)benzo[b]thiophen-5-yl)benzoic acid

HRID 44028

Reaction equation

HRID 44028 reaction equation
FC(F)(F)S(O[C:7]1[CH:26]=[CH:25][C:10]2[S:11][C:12]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)=[C:13]([C:14](=[O:17])[NH:15][CH3:16])[C:9]=2[CH:8]=1)(=O)=O.B([C:32]1[CH:33]=[C:34]([CH:38]=[CH:39][CH:40]=1)[C:35]([OH:37])=[O:36])(O)O.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>O>[F:24][C:21]1[CH:22]=[CH:23][C:18]([C:12]2[S:11][C:10]3[CH:25]=[CH:26][C:7]([C:32]4[CH:33]=[C:34]([CH:38]=[CH:39][CH:40]=4)[C:35]([OH:37])=[O:36])=[CH:8][C:9]=3[C:13]=2[C:14](=[O:17])[NH:15][CH3:16])=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 27339573-Carboxyphenylboronic acidHCID 592336822-(4-Fluorophenyl)-3-(methylcarbamoyl)benzo[b]thiophen-5-yl trifluoromethanesulfonate

Product 1

HCID 592338473-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)benzo[b]thiophen-5-yl)benzoic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

To a degassed solution containing 2-(4-fluorophenyl)-3-(methylcarbamoyl)benzo[b]thiophen-5-yl trifluoromethanesulfonate (0.32 g, 0.74 mmol), 3-boronobenzoic acid (0.18 g, 1.1 mmol), cesium carbonate (0.36 g, 1.1 mmol), dioxane (6.2 mL) and water (1.2 mL) was added tetrakis(tiphenylphosphine)palladium(0) (0.02 g, 0.016 mmol). The solution was maintained at 95° C. for 90 min. The solution was cooled to room temperature, concentrated and suspended in ethyl acetate (20 mL) with stirring for 1 h. The mixture was filtered, washed with water (3×20 mL) and air dried to afford 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzo[b]thiophen-5-yl)benzoic acid as a grey solid which was used without further purification. LCMS: retention time: 2.132 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 10 micron, 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 4 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where solvent A was 10% CH3CN/90% H2O/10 mM TFA and solvent B was 10% H2O/90% CH3CN/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 406 (MH+).

Workup

  1. temperatureThe solution was cooled to room temperature
  2. concentrationconcentrated
  3. filtrationThe mixture was filtered
  4. washwashed with water (3×20 mL) and air
  5. customdried

Sources & evidence

ORD record
ord-37ea0d3102444bbcb15b451ace17cb05
Source dataset
uspto-grants-2013_09
Patent number
US08536338B2

Linked notes

Loading…