Tribromoborane-methyl sulfide → 2-(4-fluorophenyl)-5-hydroxy-N-methylbenzo[b]thiophene-3-carboxamide

HRID 219347Notes

Reaction equation

HRID 219347 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]3[CH:13]=[CH:14][C:15]([O:17]C)=[CH:16][C:10]=3[C:9]=2[C:19]([NH:21][CH3:22])=[O:20])=[CH:4][CH:3]=1.[B-](Br)(Br)(Br)[S+](C)C>ClCCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]3[CH:13]=[CH:14][C:15]([OH:17])=[CH:16][C:10]=3[C:9]=2[C:19]([NH:21][CH3:22])=[O:20])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 4181510Tribromoborane-methyl sulfideHCID 592337112-(4-fluorophenyl)-5-methoxy-N-methylbenzo[b]thiophene-3-carboxamide

Product 1

HCID 592336552-(4-fluorophenyl)-5-hydroxy-N-methylbenzo[b]thiophene-3-carboxamide

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
83 °C

Procedure

To a suspension containing 2-(4-fluorophenyl)-5-methoxy-N-methylbenzo[b]thiophene-3-carboxamide (0.58 g, 1.8 mmol) and DCE (18 mL), was added boron tribromide-methylsulfide complex (2.3 g, 7.4 mmol) in one portion. The mixture was stirred in a closed vessel at 83° C. for 9 h under a nitrogen atmosphere, cooled to room temperature and quenched with aqueous HCl (20 mL, 1.0 N). The mixture was concentrated to remove all solvent and water was added (50 mL). The aqueous mixture was extracted with ethyl acetate (3×20 mL), dried over MgSO4, filtered and concentrated to afford 2-(4-fluorophenyl)-5-hydroxy-N-methylbenzo[b]thiophene-3-carboxamide as a tan solid which was used without further purification. 1H NMR (500 MHz, DMSO-D6) δ ppm 9.56 (s, 1H), 8.31 (d, J=4.58 Hz, 1H), 7.78 (d, J=8.55 Hz, 1H), 7.55-7.63 (m, 2H), 7.29-7.37 (m, 2H), 7.08 (d, J=2.14 Hz, 1H), 6.91 (dd, J=8.85, 2.44 Hz, 1H), 2.73 (d, J=4.58 Hz, 3H). LCMS: retention time: 2.137 mM. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 10 micron, C18, 4.6×50 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 mM where solvent A was 5% CH3CN/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% CH3CN/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 302 (MH+).

Workup

  1. temperaturecooled to room temperature
  2. customquenched with aqueous HCl (20 mL, 1.0 N)
  3. concentrationThe mixture was concentrated
  4. customto remove all solvent and water
  5. additionwas added (50 mL)
  6. extractionThe aqueous mixture was extracted with ethyl acetate (3×20 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-885f701f881643db8cf733e9cb773dd0
Source dataset
uspto-grants-2012_06
Patent number
US08198449B2

Reaction notes

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