Hydrochloric Acid → HCID 59275394, compound

HRID 555100Notes

Reaction equation

HRID 555100 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]([O:25]C)=[O:24])=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1.C[Si](C)(C)[O-].[K+].O1CCCC1.ClCCl.Cl>ClCCl.CO.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]([OH:25])=[O:24])=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 21919333Tetrahydrofurane dichloromethaneHCID 23668039Potassium trimethylsilanolateHCID 59275552HCID 59275552, compound

Product 1

HCID 59275394HCID 59275394, compoundYield 91%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a 50 mL round-bottomed flask was added methyl 2-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yloxy)acetate (132.3 mg, 0.370 mmol) and 2 equivalents of potassium trimethylsilanolate (95 mg, 0.740 mmol) along with a 1:1 solution of tetrahydrofuran/dichloromethane (10 ml) to give a yellow heterogeneous mixture. The mixture was stirred at room temperature overnight. The crude product was then cooled to 0° C., diluted further with dichloromethane, and acidified with 1 N HCl. The product was extracted, washed with water then brine, and dried over magnesium sulfate. After solvent evaporation, the product was triturated with hexane to give a 91% yield (115 mgs), a white amorphous solid after drying under vacuum. The LC/MS data was obtained on a Shimadzu analytical LC/MICROMASS® Platform LC (ESI+) at 220 nm using the following set of conditions: PHENOMENEX® 10 μm C18, 4.6×30 mm column, with a gradient of 0-100% B (B=90% HPLC grade methanol/0.1% trifluoroacetic acid/10% HPLC grade water), (A=90% HPLC grade water/0.1% trifluoroacetic acid/10% HPLC grade methanol), in 2 minutes with a 1 minute hold at a rate of 5 mL/minute. The NMR spectra was recorded at room temperature using a Bruker DRX300 spectrometer. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.82 (d, J=4.39 Hz, 3H), 4.72 (s, 2H), 7.00 (dd, J=8.78, 2.56 Hz, 1H), 7.08 (d, J=2.56 Hz, 1H), 7.35 (t, J=8.97 Hz, 2H), 7.57 (d, J=8.78 Hz, 1H), 7.92 (dd, J=8.78, 5.49 Hz, 2H), 8.34 (m, 1H). LCMS m/z 344.27 (M+H), Rt 1.450 min., 96.0% purity.

Workup

  1. customto give a yellow heterogeneous mixture
  2. extractionThe product was extracted
  3. washwashed with water
  4. dry with materialbrine, and dried over magnesium sulfate
  5. customAfter solvent evaporation
  6. customthe product was triturated with hexane
  7. customto give a 91% yield (115 mgs)
  8. customa white amorphous solid after drying under vacuum
  9. customThe LC/MS data was obtained on a Shimadzu analytical LC/MICROMASS® Platform LC (ESI+) at 220 nm
  10. customwas recorded at room temperature

Sources & evidence

ORD record
ord-5ae24447df574e13bc1ac6e3dd40241d
Source dataset
uspto-grants-2011_11
Patent number
US08048887B2

Reaction notes

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