Dimethylformamide → 6-Fluoro-1-tetrahydropyran-2-yl-indazole-4-carbaldehyde

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Reaktionsgleichung

C([Li])CCC.Br[C:7]1[CH:15]=[C:14]([F:16])[CH:13]=[C:12]2[C:8]=1[CH:9]=[N:10][N:11]2[CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][O:18]1.CN([CH:26]=[O:27])C>C1COCC1>[F:16][C:14]1[CH:15]=[C:7]([CH:26]=[O:27])[C:8]2[CH:9]=[N:10][N:11]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[C:12]=2[CH:13]=1

Komponenten

Reaktionsbedingungen

Temperatur: -40 °C

Versuchsvorschrift

To a solution of n-butyllithium (13 mL, 21.4 mmol, 1.6 M in hexanes) in THF (60 mL) at −78° C. was added dropwise over 30 min a solution of 4-bromo-6-fluoro-1-tetrahydropyran-2-yl-indazole (4.00 g, 13.4 mmol) in THF (20 mL). The reaction was warmed to −40° C. for 5 min, re-cooled to −78° C., and DMF (4.2 mL, 53.5 mmol) was added. The reaction mixture was allowed to warm to RT and stirred for 2 h. The reaction was then quenched with a satd. aq. NH4Cl at 0° C. EtOAc was added and the layers were separated, and the aqueous layer was extracted once with EtOAc. The combined extracts were dried (Na2SO4), filtered and concentrated in vacuo. The crude mixture was purified by SiO2 chromatography to afford 6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-4-carbaldehyde (2.18 g, 66%), as a white solid. MS (ESI) m/z: 249.3 [M+1]+.

Aufarbeitung

temperaturere-cooled to −78° C.
temperatureto warm to RT
customThe reaction was then quenched with a satd
customat 0° C
additionEtOAc was added
customthe layers were separated
extractionthe aqueous layer was extracted once with EtOAc
dry with materialThe combined extracts were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude mixture was purified by SiO2 chromatography

Quellen und Nachweise

ORD-Eintrag: ord-a766bfe82d184a55bdf92e4580d6861f
Quelldatensatz: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08637537B2

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