Hydrochloric Acid → ({1-[(3-Hydroxyphenyl)ethynyl]-2-naphthyl}oxy)acetic acid

HRID 2390369Notes

Reaction equation

HRID 2390369 reaction equation
C([O:5][C:6](=[O:20])[CH2:7][O:8][C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]=1Br)(C)(C)C.[OH:21][C:22]1[CH:23]=[C:24]([C:28]#[CH:29])[CH:25]=[CH:26][CH:27]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1CCCCC1.Cl>O.CC(C)=O.C(Cl)Cl.O1CCOCC1.[Pd](Cl)Cl>[OH:21][C:22]1[CH:23]=[C:24]([C:28]#[C:29][C:10]2[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH:17]=[CH:18][C:9]=2[O:8][CH2:7][C:6]([OH:5])=[O:20])[CH:25]=[CH:26][CH:27]=1

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 8082PiperidineHCID 11776TriphenylphosphineHCID 139144m-EthynylphenolHCID 58522023tert-Butyl[(1-bromo-2-naphthyl)oxy]acetate2×

Product 1

HCID 46865199({1-[(3-Hydroxyphenyl)ethynyl]-2-naphthyl}oxy)acetic acid

Reagents, catalysts & solvents 5

HCID 24290Palladium ChlorideCatalystHCID 180AcetoneSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (1-bromo-naphthalen-2-yloxy)-acetic acid tert-butyl ester (Intermediate 217, 125 mg; 0.37 mmol), 3-hydroxyphenylacetylene (53 mg; 0.44 mmol), palladium(II) chloride (3.3 mg; 0.02 mmol), triphenylphosphine (10 mg; 0.04 mmol) and piperidine (73 μl; 0.74 mmol) in distilled water (1.1 ml) and Acetone (1.4 ml) was stirred overnight at 60° C. The reaction mixture was extracted by EtOAc and the organic phases was dried over MgSO4, concentrated to dryness and purified by preparative HPLC. The intermediate obtained was diluted in DCM (1 ml) and treated with a 4 M solution of HCl in dioxane (930 μl). After stirring overnight, the reaction mixture was concentrated to dryness and purified by preparative HPLC to afford the title compound as a beige solid.

Workup

  1. extractionThe reaction mixture was extracted by EtOAc
  2. dry with materialthe organic phases was dried over MgSO4
  3. concentrationconcentrated to dryness
  4. custompurified by preparative HPLC
  5. customThe intermediate obtained
  6. stirringAfter stirring overnight
  7. concentrationthe reaction mixture was concentrated to dryness
  8. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-96953d28d6ea48d583122c2b837410c7
Source dataset
uspto-grants-2012_09
Patent number
US08273769B2

Reaction notes

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