Oxazole → N-Methyl-5-oxazol-2-yl-N-propyl-isophthalamic acid

HRID 348858

Reaktionsgleichung

Reaktionsgleichung von HRID 348858
[O:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])CCC.I[C:12]1[CH:13]=[C:14]([CH:19]=[C:20]([C:22]([N:24]([CH3:28])[CH2:25][CH2:26][CH3:27])=[O:23])[CH:21]=1)[C:15]([O:17]C)=[O:16].O.[OH-].[Li+]>O1CCCC1.C(OCC)(=O)C.O1CCCC1.CO.O.C(Cl)(Cl)Cl.[Cl-].[Zn+2].[Cl-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH3:28][N:24]([CH2:25][CH2:26][CH3:27])[C:22]([C:20]1[CH:19]=[C:14]([CH:13]=[C:12]([C:2]2[O:1][CH:5]=[CH:4][N:3]=2)[CH:21]=1)[C:15]([OH:17])=[O:16])=[O:23]

Komponenten

11

Edukt 4

HCID 9255OxazoleHCID 168937Lithium hydroxide, monohydrateHCID 21086185Methyl 3-iodo-5-{[methyl(propyl)amino]carbonyl}benzoateHCID 178418339Butyllithium

Produkt 1

HCID 21085840N-Methyl-5-oxazol-2-yl-N-propyl-isophthalamic acid

Reagenzien, Katalysatoren, Lösungsmittel 6

HCID 3007855ZincchlorideKatalysatorHCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 6212ChloroformLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittelHCID 21892291Methanol tetrahydrofuran waterLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a −70° C. stirred solution of oxazole (330 mg, 4.8 mmol) in tetrahydrofuran (4 mL) is added n-butyllithium (1.6 M in hexanes, 3.3 mL, 5.3 mmol). After 30 min, zinc chloride (1 M in diethyl ether, 14.5 mL, 14.5 mmol) is added and the reaction mixture is warmed to 0° C. for 1 h. To this mixture is added a solution of methyl 3-iodo-5-{[methyl(propyl)amino]carbonyl}benzoate (1.6 g, 4.5 mmol) in anhydrous tetrahydrofuran (3 mL) followed by palladium(0) tetrakis(triphenylphosphine) (221 mg, 0.19 mmol). The reaction mixture is heated at reflux for 2 h. The reaction mixture is cooled, diluted with ethyl acetate, washed with water, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 60% ethyl acetate/hexane) provides a solid. The solid is redissolved in 1:1:1 tetrahydrofuran/methanol/water (9 mL), and lithium hydroxide monohydrate (311 mg, 7.4 mmol) is added and stirred 2 h at room temperature. The reaction is diluted in chloroform and washed with 1N hydrochloric acid (aq), water, and brine, dried (sodium sulfate), filtered and concentrated under reduced pressure to give the title compound. ESI MS m/z 287.3 [M−H]−.

Aufarbeitung

  1. temperatureThe reaction mixture is heated
  2. temperatureat reflux for 2 h
  3. temperatureThe reaction mixture is cooled
  4. washwashed with water, and brine
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash column chromatography (silica gel, 60% ethyl acetate/hexane)
  9. customprovides a solid
  10. additionis added
  11. washwashed with 1N hydrochloric acid (aq), water, and brine
  12. dry with materialdried (sodium sulfate)
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-ed6d8604e6304f23b4ab4738459a30fb
Quelldatensatz
uspto-grants-2007_02
Patentnummer
US07176242B2

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