Ammonium Chloride → (3-Fluorophenyl)-(3-fluoropyridin-2-yl)-methanol

HRID 33999

Reaction equation

C([Li])CCC.[F:6][C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1.[F:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=1)[CH:17]=[O:18].[Cl-].[NH4+]>C(OCC)C.CCCCCC.C(OCC)(=O)C>[F:13][C:14]1[CH:15]=[C:16]([CH:17]([C:8]2[C:7]([F:6])=[CH:12][CH:11]=[CH:10][N:9]=2)[OH:18])[CH:19]=[CH:20][CH:21]=1

Participants

Conditions

Temperature: -20 °C

Procedure

Under nitrogen atmosphere, a solution of 9.75 g of diazabicyclo[2.2.0]octane in 150 mL of dehydrated diethyl ether was cooled to −40° C., added with 56 mL of 1.56 M n-butyllithium in hexane, and stirred at −20° C. for 1 hour. The solution was cooled to-60° C., added dropwise with 6.9 mL of 3-fluoropyridine, stirred at −60° C. for 1 hour, and added with 9.2 mL of 3-fluorobenzaldehyde. After stirring for 1 hour, aqueous ammonium chloride and ethyl acetate were successively added, and the mixture was recovered to room temperature. The organic layer was extracted, washed with water, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the resulting crude product was purified and separated by silica gel column chromatography (ethyl acetate:hexane=1:4), to give 12.6 g of the title compound as colorless needle crystals.

Workup

temperatureThe solution was cooled to-60° C.
stirringstirred at −60° C. for 1 hour
stirringAfter stirring for 1 hour
customthe mixture was recovered to room temperature
extractionThe organic layer was extracted
washwashed with water
dry with materialdried over anhydrous magnesium sulfate
customThe solvent was evaporated
customthe resulting crude product was purified
customseparated by silica gel column chromatography (ethyl acetate:hexane=1:4)

Sources & evidence

ORD record: ord-301457584e034ef78be9b798feba0750
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07429609B2

Linked notes

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