Diethyl Ether → 6-(4-Fluoro-benzyloxy)-pyridine-3-carbaldehyde

HRID 77939Notes

Reaction equation

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

Participants

Conditions

Temperature: -78 °C

Procedure

To a diethyl ether (150 mL) solution of 5-bromo-2-(4-fluoro-benzyloxy)-pyridine (3.75 g 13.3 mmol) described in Manufacturing Example 58-1-1 was added n-butyl lithium (2.55 M n-hexane solution, 6.26 mL, 16.0 mmol) on a dry ice-ethanol bath (−78° C.) under nitrogen atmosphere, which was stirred for 30 minutes at −78° C. N,N-dimethylformamide (1.54 mL, 20.0 mmol) was then added dropwise and stirred for 5 minutes at −78° C. The reaction solution was allowed to room temperature, water was added, and the solution was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:3) to obtain the title compound (2.23 g, 72.5%).

Workup

stirringstirred for 5 minutes at −78° C
customwas allowed to room temperature
extractionthe solution was extracted with ethyl acetate
washThe organic layer was washed with saturated aqueous sodium chloride
customthe solvent was evaporated under a reduced pressure
customThe residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:3)

Sources & evidence

ORD record: ord-21a50570643f405dac5799be6d8831db
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841327B2

Reaction notes

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