Nitrogen → 6-{4-[5-Cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-2-methyl-phenyl}-2-methyl-benzofuran-3-carboxylic acid methyl ester

HRID 250296

Reaktionsgleichung

Reaktionsgleichung von HRID 250296
[CH3:1][O:2][C:3]([C:5]1[C:9]2[CH:10]=[CH:11][C:12](B3OC(C)(C)C(C)(C)O3)=[CH:13][C:8]=2[O:7][C:6]=1[CH3:23])=[O:4].Br[C:25]1[CH:48]=[CH:47][C:28]([O:29][CH2:30][C:31]2[C:32]([C:39]3[C:44]([Cl:45])=[CH:43][CH:42]=[CH:41][C:40]=3[Cl:46])=[N:33][O:34][C:35]=2[CH:36]2[CH2:38][CH2:37]2)=[CH:27][C:26]=1[CH3:49].N#N.C1(P(C2CCCCC2)C2(OC)CC=CC(OC)=C2C2C=CC=CC=2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][O:2][C:3]([C:5]1[C:9]2[CH:10]=[CH:11][C:12]([C:25]3[CH:48]=[CH:47][C:28]([O:29][CH2:30][C:31]4[C:32]([C:39]5[C:44]([Cl:45])=[CH:43][CH:42]=[CH:41][C:40]=5[Cl:46])=[N:33][O:34][C:35]=4[CH:36]4[CH2:38][CH2:37]4)=[CH:27][C:26]=3[CH3:49])=[CH:13][C:8]=2[O:7][C:6]=1[CH3:23])=[O:4]

Komponenten

9

Edukt 5

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 574433422-Methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzofuran-3-carboxylic acid methyl esterHCID 665453372-Dicyclohexylphosphino-2,6-dimethoxybiphenylHCID 672715854-(4-Bromo-3-methyl-phenoxymethyl)-5-cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazole

Produkt 1

HCID 672723176-{4-[5-Cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-2-methyl-phenyl}-2-methyl-benzofuran-3-carboxylic acid methyl esterAusbeute 55 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A solution of 2-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzofuran-3-carboxylic acid methyl ester (0.145 g, 0.459 mmol) and 4-(4-bromo-3-methyl-phenoxymethyl)-5-cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazole (229 mg, 0.504 mmol) in toluene (5 mL) is evacuated and refilled with N2 three times. Pd(OAc)2 (10 mg), 2-dicyclohexylphosphino-2,6-dimethoxy-1,1′-biphenyl (38 mg) and potassium phosphate, tribasic, N-hydrate (195 mg) in water (0.5 mL) are added. The resulting mixture is evacuated and refilled with N2 three times and stirred at 110° C. for 16 hours. The mixture is cooled to room temperature and filtered through a pad of diatomaceous earth. The filtrate is concentrated to a residue. The residue is purified via silica gel chromatography eluting with 25% EtOAc/Hexanes to provide the title compound (0.14 g, 55%). 1H NMR (400 MHz, CDCl3): 7.90 (d, 1H), 7.39 (d, 1H), 7.37 (s, 1H), 7.31-7.29 (m, 2H), 7.18 (d, 1H), 7.10 (d, 1H), 6.70-6.66 (m, 2H), 4.80 (s, 2H), 3.94 (s, 3H), 2.76 (s, 3H), 2.18 (s, 3H), 2.17 (m, 1H), 1.29-1.25 (m, 2H), 1.15-1.11 (m, 2H).

Aufarbeitung

  1. customThe resulting mixture is evacuated
  2. additionrefilled with N2 three times
  3. temperatureThe mixture is cooled to room temperature
  4. filtrationfiltered through a pad of diatomaceous earth
  5. concentrationThe filtrate is concentrated to a residue
  6. customThe residue is purified via silica gel chromatography
  7. washeluting with 25% EtOAc/Hexanes

Quellen und Nachweise

ORD-Eintrag
ord-518b06894b764e74816bb608342aa2db
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07863302B2

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