Dichloromethane → tert-Butyl 3-(5-methylpyridin-2-yl)-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzoate

HRID 1257530Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1257530
Br[C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([C:15]2[CH2:19][C@@H:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=3)[O:17][N:16]=2)[CH:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[Br-].[CH3:27][C:28]1[CH:29]=[CH:30][C:31]([Zn+])=[N:32][CH:33]=1.[K+].[K+].[K+].C(N(CC([O-])=O)CC(O)=O)CN(CC([O-])=O)CC([O-])=O.ClCCl>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:27][C:28]1[CH:29]=[CH:30][C:31]([C:2]2[CH:3]=[C:4]([CH:12]=[C:13]([C:15]3[CH2:19][C@@H:18]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=4)[O:17][N:16]=3)[CH:14]=2)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6])=[N:32][CH:33]=1

Komponenten

7

Edukt 4

HCID 6344DichloromethaneHCID 62717Edetate TripotassiumHCID 58096179tert-butyl 3-bromo-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzoateHCID 178427808HCID 178427808, Verbindung

Produkt 1

HCID 66895837tert-Butyl 3-(5-methylpyridin-2-yl)-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzoateAusbeute 90,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418851HCID 178418851, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

To a solution of tert-butyl 3-bromo-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzoate (19.95 g, 49.5 mmol) and bis(tri-tert-butylphosphine)palladium(0) (0.76 g, 1.48 mmol) in dioxane (247 mL) was added 5-methyl-2-pyridylzinc bromide (0.5 M in THF; 198 mL, 99 mmol). The reaction mixture was heated to 75° C. After 1 h, the reaction was cooled to ambient temperature. Aqueous ethylenediaminetetraacetic acid tripotassium salt (0.4 M, 200 mL) and dichloromethane (200 mL) were added. The mixture was stirred for 15 min and the organic solvent was evaporated. The mixture was extracted with dichloromethane (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% ethyl acetate 98% ethyl acetate/methanol) gave the title compound (18.6 g). MS 416.1 (M+1).

Aufarbeitung

  1. temperaturethe reaction was cooled to ambient temperature
  2. customthe organic solvent was evaporated
  3. extractionThe mixture was extracted with dichloromethane (3×)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (100% ethyl acetate 98% ethyl acetate/methanol)

Quellen und Nachweise

ORD-Eintrag
ord-a0b70897865d482a814efc7fdc0b37bd
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08461185B2

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