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

HRID 640277Notes

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-fe7776912856481da353cdf49049eeb1
Source dataset: uspto-grants-2010_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07691882B2

Reaction notes

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