4-Fluoroanisole → (2-Fluoro-5-methoxy-phenyl)-4-pyridylmethanol

HRID 260712

Reaction equation

C([Li])CCC.CN(C)CCN(C)CCN(C)C.[F:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1.[N:27]1[CH:32]=[CH:31][C:30]([CH:33]=[O:34])=[CH:29][CH:28]=1>C1COCC1>[F:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=1[CH:33]([C:30]1[CH:31]=[CH:32][N:27]=[CH:28][CH:29]=1)[OH:34]

Participants

Conditions

Temperature: -75 °C

Procedure

Butyllithium (47.5 ml of 2.22M solution, 106 mmol) was added slowly to a solution of pentamethyldiethylenetriamine (15 ml) and 4-fluoroanisole (12.61 g, 0.1 mol) in THF (150 ml) at -70° C. The solution was stirred for 2 hr at -75° C. and a solution of pyridine-4-carboxaldehyde (9.55 ml, 0.1 mol) in THF was added at -75° C. The mixture was allowed to warm to 25° C. slowly and then quenched with ammonium chloride solution. The mixture was diluted with ethyl acetate and the organic layer was separated. The organic layer was washed with water and 3N hydrochloric acid. The acid washes were then basified with sodium hydroxide and extracted with ether and the ether solution concentrated in vacuo. The crude product was recrystallized from 80% ethanol to give (2-fluoro-5-methoxy-phenyl)-4-pyridylmethanol as a white powder (12.22 g+3.12 g second crop, 66% total yield).

Workup

temperatureto warm to 25° C. slowly
customquenched with ammonium chloride solution
additionThe mixture was diluted with ethyl acetate
customthe organic layer was separated
washThe organic layer was washed with water and 3N hydrochloric acid
extractionextracted with ether
concentrationthe ether solution concentrated in vacuo
customThe crude product was recrystallized from 80% ethanol
customto give

Sources & evidence

ORD record: ord-f7369bd798fe427f9da8b2f62d1b2dc9
Source dataset: uspto-grants-1996_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05530012

Linked notes

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