Hydrochloric Acid → HCID 59233734, compound

HRID 219345Notes

Reaction equation

HRID 219345 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][CH3:18])=[CH:16][C:10]=3[C:9]=2[C:19]([O:21]C)=[O:20])=[CH:4][CH:3]=1.C1COCC1.[OH-].[Li+].Cl>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:12][C:11]3[CH:13]=[CH:14][C:15]([O:17][CH3:18])=[CH:16][C:10]=3[C:9]=2[C:19]([OH:21])=[O:20])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 59233701HCID 59233701, compound

Product 1

HCID 59233734HCID 59233734, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a solution containing methyl 2-(4-fluorophenyl)-5-methoxybenzo[b]thiophene-3-carboxylate (0.59 g, 1.9 mmol), THF (13.5 mL) and methanol (8.5 mL) was added aqueous lithium hydroxide (9.3 mL, 2.0 M). The solution was maintained at 50° C. for 15 h. The solution was cooled to room temperature, adjusted to below pH 4 with aqueous HCl (22 mL, 1.0 N) and extracted with ethyl acetate (3×15 mL). The combined organic portions were washed with brine (15 mL), dried over MgSO4, filtered and concentrated to afford 2-(4-fluorophenyl)-5-methoxybenzo[b]thiophene-3-carboxylic acid as white solid which was used without further purification. 1H NMR (500 MHz, DMSO-D6) δ ppm 12.99 (s, 1H), 7.93 (d, J=8.55 Hz, 1H), 7.80 (d, J=2.44 Hz, 1H), 7.59 (dd, J=8.55, 5.49 Hz, 2H), 7.32 (t, J=8.70 Hz, 2H), 7.11 (dd, J=8.85, 2.44 Hz, 1H), 3.82-3.87 (m, 3H). LCMS: retention time: 1.532 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 303 (MH+).

Workup

  1. temperatureThe solution was cooled to room temperature
  2. extractionextracted with ethyl acetate (3×15 mL)
  3. washThe combined organic portions were washed with brine (15 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-5ca2ade9de064347a67bbdc07175ca42
Source dataset
uspto-grants-2012_06
Patent number
US08198449B2

Reaction notes

Loading…