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

HRID 2260501Notes

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

Butyl lithium (47.5 ml of 2.22M solution, 105.6 mmole) was added slowly to a solution of pentamethyldiethylenetriamine (15 ml) and 4-fluoroanisole (12.61 g, 0.1 mole) in THF (150 ml) at -70° C. The solution was stirred for 2 hr at -75° C. and a solution of pyridine-4-aldehyde (9.55 ml, 0.1 mole) 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, 65.8% 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-0f8b2461e58941858af9189ab10f6a54
Source dataset: uspto-grants-1995_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05478828

Reaction notes

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