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

HRID 475312Notes

Reaction equation

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

Participants

Conditions

Temperature: -40 °C

Procedure

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]+.

Workup

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

Sources & evidence

ORD record: ord-a766bfe82d184a55bdf92e4580d6861f
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637537B2

Reaction notes

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