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

HRID 44027Notes

Reaction equation

HRID 44027 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 min. 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 min 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-d429899f1bb34f35a81b469e3ed37d6b
Source dataset
uspto-grants-2013_09
Patent number
US08536338B2

Reaction notes

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