Hydrochloric Acid → 4-Hydroxy-7-phenoxy-1-phenyl-isoquinoline-3-carboxylic acid methyl ester

HRID 1481178Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1481178
[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7](Br)[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:9]=2)=[O:4].[C:24]1(B(O)O)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C([O-])([O-])=O.[Cs+].[Cs+].Cl>CN(C=O)C.[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(C)=O>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:9]=2)=[O:4]

Komponenten

9

Edukt 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 66827Phenylboronic AcidHCID 89813003Methyl 1-bromo-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

Produkt 1

HCID 898129524-Hydroxy-7-phenoxy-1-phenyl-isoquinoline-3-carboxylic acid methyl esterAusbeute 66 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 1-bromo-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (150 mg, 0.40 mmol), phenylboronic acid (60 mg, 0.48 mmol), Pd(PPh3)4 (46 mg, 0.040 mmol) and Cs2CO3 (261 mg, 0.80 mmol) in DMF (4 mL) was heated at 100° C. for 16 h under N2 atmosphere. After cooling the mixture to r.t., brine (20 mL) and EtOAc (50 mL) were added. 1 M HCl was added with stirring until pH was ˜2. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, washed with water, and dried over MgSO4. After evaporating the solvent, the crude product was purified by column chromatography (0-25% EtOAc/hexanes+2% AcOH) to give 98 mg of the title compound as a white solid. MS: (+) m/z 372.09 (M+1).

Aufarbeitung

  1. temperatureAfter cooling the mixture to r.t.
  2. extractionThe aqueous layer was extracted with additional EtOAc
  3. washwashed with water
  4. dry with materialdried over MgSO4
  5. customAfter evaporating the solvent
  6. customthe crude product was purified by column chromatography (0-25% EtOAc/hexanes+2% AcOH)

Quellen und Nachweise

ORD-Eintrag
ord-4fc42d8eee144e85a86dff793f0afd4b
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09409892B2

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