Dimethylformamide → 4-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole-5-carbaldehyde

HRID 475229Notes

Reaction equation

Br[C:2]1[CH:16]=[CH:15][C:5]2[N:6]([CH:9]3[CH2:14][CH2:13][CH2:12][CH2:11][O:10]3)[CH:7]=[N:8][C:4]=2[C:3]=1[F:17].CCCCCC.CN([CH:27]=[O:28])C>C1COCC1>[F:17][C:3]1[C:4]2[N:8]=[CH:7][N:6]([CH:9]3[CH2:14][CH2:13][CH2:12][CH2:11][O:10]3)[C:5]=2[CH:15]=[CH:16][C:2]=1[CH:27]=[O:28]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 146 (10 g, 0.034 mol) in dry THF (100 mL) at −78° C. was added dropwise 1.6 M N-butyl lithium solution in hexane (23 mL, 0.0374 mol). After stirring for 45 min at −78° C., a solution of DMF (5 g, 0.068 mol) in THF (20 mL) was added dropwise. After 1 h at −78° C. the reaction mixture was quenched slowly by adding water. The aqueous phase separated was extracted with EtOAc and the combined organic extracts washed with water and brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with 15% EtOAc/petroleum ether to afford 7.7 g (93%) of 4-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole-5-carbaldehyde (148) as a yellow solid.

Workup

customAfter 1 h at −78° C. the reaction mixture was quenched slowly
additionby adding water
customThe aqueous phase separated
extractionwas extracted with EtOAc
washthe combined organic extracts washed with water and brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified by SiO2 chromatography
washeluting with 15% EtOAc/petroleum ether

Sources & evidence

ORD record: ord-618a45e911274026b82c9329ef89eb81
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637537B2

Reaction notes

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