Diethyl Ether → 6-(4-Fluorophenoxymethyl)-pyridine-3-carbaldehyde

HRID 1691100Notes

Reaction equation

[CH2:1]([O:3]CC)C.Br[C:7]1[CH:8]=[CH:9][C:10]([CH2:13][O: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]([O:14][CH2:13][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 (100 mL) solution of 5-bromo-2-(4-fluoro-phenoxymethyl)-pyridine (4.00 g, 14.2 mmol) described in Manufacturing Example 72-1-1 was added dropwise n-butyl lithium (2.55 M n-hexane solution, 6.13 mL, 15.6 mmol) on a dry ice-ethanol bath (−78° C.) under nitrogen atmosphere, which was stirred for 40 minutes at −78° C. N,N-dimethylformamide (1.32 mL, 17.0 mmol) was then added dropwise and stirred for 5 minutes at −78° C. The reaction solution was cooled to room temperature and water was added, followed by extraction 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=1:4) to obtain the title compound (1.00 g, 30.5%).

Workup

stirringstirred for 5 minutes at −78° C
temperatureThe reaction solution was cooled to room temperature
extractionfollowed by extraction 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=1:4)

Sources & evidence

ORD record: ord-4ede03ad562449e082656e4d2a575812
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08153662B2

Reaction notes

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