Bromomethylcyclopropane → HCID 16722641, Verbindung

HRID 2421109Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2421109
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH2:26])[CH:6]=[CH:7][C:8]=1[C:9]1[O:10][C:11]([C:14]2[C:15]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[N:16][O:17][C:18]=2[CH3:19])=[N:12][N:13]=1.C(N(CC)C(C)C)(C)C.Br[CH2:37][CH:38]1[CH2:40][CH2:39]1.C[Si]([N-][Si](C)(C)C)(C)C.[K+]>C1COCC1>[CH:38]1([CH2:37][NH:26][C:5]2[CH:6]=[CH:7][C:8]([C:9]3[O:10][C:11]([C:14]4[C:15]([C:20]5[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=5)=[N:16][O:17][C:18]=4[CH3:19])=[N:12][N:13]=3)=[C:3]([O:2][CH3:1])[CH:4]=2)[CH2:40][CH2:39]1

Komponenten

6

Edukt 4

HCID 81503Bromomethylcyclopropane3×HCID 81531DiisopropylethylamineHCID 3251421Potassium bis(trimethylsilyl)amideHCID 167225873-Methoxy-4-[5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazol-2-yl]-phenylamine

Produkt 1

HCID 16722641HCID 16722641, VerbindungAusbeute 15 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a suspension of 3-methoxy-4-[5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazol-2-yl]-phenylamine (200 mg, 0.57 mmol) in THF was added N,N-diisopropyl ethyl amine (128 μL, 0.75 mmol) and bromomethyl-cyclopropane (61 μL, 0.63 mmol) and the reaction mixture was stirred for 24 h at ambient temperature. After addition of potassium bis(trimethylsilyl)amide (0.91 M in THF, 0.82 mL, 0.75 mmol) was added stirring was continued for 15 min and further bromomethyl-cyclopropane (78 μL, 0.80 mmol) was added. After stirring for 18 h at ambient temperature further bromomethyl-cyclopropane (0.12 mL, 1.2 mmol) was added and stirring continued for 24 h at this temperature. The reaction mixture was extracted with aqueous sodium carbonate (saturated, 20 mL) and ethyl acetate (20 mL). The aqueous layer was extracted with ethyl acetate (20 mL) and the combined organic layers dried over sodium sulfate. Concentration and then purification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane=40:40:20 to 0:80:20) afforded the title compound (34 mg, 15%) as a light brown solid. MS: m/e=403.4 [M+H]+.

Aufarbeitung

  1. additionwas added
  2. stirringstirring
  3. waitwas continued for 15 min
  4. additionwas added
  5. stirringstirring
  6. waitcontinued for 24 h at this temperature
  7. extractionThe reaction mixture was extracted with aqueous sodium carbonate (saturated, 20 mL) and ethyl acetate (20 mL)
  8. extractionThe aqueous layer was extracted with ethyl acetate (20 mL)
  9. dry with materialthe combined organic layers dried over sodium sulfate
  10. concentrationConcentration
  11. custompurification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane=40:40:20 to 0:80:20)

Quellen und Nachweise

ORD-Eintrag
ord-d73dd857c2c6409ba4f92709a7ff4a84
Quelldatensatz
uspto-grants-2011_06
Patentnummer
US07956074B2

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