Hydrochloric Acid → HCID 90372445, compound

HRID 632703Notes

Reaction equation

HRID 632703 reaction equation
[F:1][CH:2]([F:35])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[S:13][C:12]2[CH:14]=[C:15]([OH:18])[CH:16]=[CH:17][C:11]=2[C:10]=1[O:19][C:20]1[CH:25]=[CH:24][C:23](/[CH:26]=[CH:27]/[C:28]([O:30]C(C)(C)C)=[O:29])=[CH:22][CH:21]=1.Cl>O1CCOCC1>[F:35][CH:2]([F:1])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[S:13][C:12]2[CH:14]=[C:15]([OH:18])[CH:16]=[CH:17][C:11]=2[C:10]=1[O:19][C:20]1[CH:25]=[CH:24][C:23](/[CH:26]=[CH:27]/[C:28]([OH:30])=[O:29])=[CH:22][CH:21]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 118574971HCID 118574971, compound

Product 1

HCID 90372445HCID 90372445, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of afford (E)-tert-butyl 3-(4-((2-(2-(difluoromethyl)phenyl)-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylate (100 mg, 0.202 mmol) in 1,4-dioxane (3.0 mL) was added 4.0M aq. HCl (0.202 mL, 0.809 mmol). The resulting mixture was warmed to 50° C. and stirred at that temperature for 2 b after which time the reaction was quenched by addition of sat. aq. NaHCO3 and extracted with EtOAc (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuo and the resulting crude material was purified by reverse phase HPLC (basic conditions, 0.1% NH4OH in CH3CN/H2O) to afford (E)-3-(4-((2-(2-(difluoromethyl)phenyl)-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid (16.7 mg, 0.037 mmol, 19% yield). 1H NMR (400 MHz, CD3OD) δ ppm=7.72-7.64 (m, 1H), 7.54-7.42 (m, 4H), 7.39 (d, J=8.7 Hz, 2H), 7.33-7.24 (m, 2H), 7.00 (d, J=55.2 Hz, 1H), 6.88 (dd, J=8.7, 2.2 Hz, 1H), 6.81 (d, J=8.9 Hz, 2H), 6.30 (d, J=16.0 Hz, 1H). HRMS (m/z, MH+): 439.0776.

Workup

  1. customwas quenched by addition of sat. aq. NaHCO3
  2. extractionextracted with EtOAc (3×)
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customthe resulting crude material was purified by reverse phase HPLC (basic conditions, 0.1% NH4OH in CH3CN/H2O)

Sources & evidence

ORD record
ord-26b985ecbf4e4ba08e7d0229527ecf8e
Source dataset
uspto-grants-2016_04
Patent number
US09321746B2

Reaction notes

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