1-Methyl-3-phenyl-1H-1,2,4-triazole → (3-(tert-butyldimethylsilyloxy)-5-ethyl-2-fluorophenyl)(2-methyl-5-phenyl-2H-1,2,4-triazol-3-yl)methanol

HRID 2105049

Reaktionsgleichung

[CH3:1][N:2]1[CH:6]=[N:5][C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:3]1.C([Li])CCC.[Si:18]([O:25][C:26]1[C:27]([F:36])=[C:28]([CH:31]=[C:32]([CH2:34][CH3:35])[CH:33]=1)[CH:29]=[O:30])([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]>C1COCC1>[Si:18]([O:25][C:26]1[C:27]([F:36])=[C:28]([CH:29]([C:6]2[N:2]([CH3:1])[N:3]=[C:4]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)[N:5]=2)[OH:30])[CH:31]=[C:32]([CH2:34][CH3:35])[CH:33]=1)([C:21]([CH3:22])([CH3:24])[CH3:23])([CH3:20])[CH3:19]

Komponenten

Reaktionsbedingungen

Temperatur: 23 °C

Versuchsvorschrift

To a solution of 1-methyl-3-phenyl-1H-1,2,4-triazole (310 mg, 1.95 mmol, see J. Chem. Soc., 1954, 3319-3322) in THF (25 mL) cooled to −78° C. was added 1.6 M n-butyl lithium (1.33 mL, 2.12 mmol) dropwise and stirred for 15 min. Next a solution of Intermediate 368.2 (500 mg, 1.77 mmol) in THF (5 mL) was added dropwise and stirred for 5 min before allowing the mixture to warm to 23° C. The mixture was quenched with aqueous NH4Cl and extracted with EtOAc (3×50 mL). The organic layer was washed with H2O, brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 60% EtOAc/hexanes gradient) to afford 440 mg of Example 368.3. HPLC (2 min gradient) RT=2.42 min.

Aufarbeitung

stirringstirred for 5 min
customThe mixture was quenched with aqueous NH4Cl
extractionextracted with EtOAc (3×50 mL)
washThe organic layer was washed with H2O, brine
dry with materialdried (Na2SO4)
concentrationconcentrated
customThe crude product was purified by flash chromatography (0 to 60% EtOAc/hexanes gradient)

Quellen und Nachweise

ORD-Eintrag: ord-2bfddfb368cc4fb48a37f28e0faafdbc
Quelldatensatz: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US07576098B2

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