4-Bromoanisole → 4-(4-Methoxyphenyl)pyridine

Temperature

-10 °C

A solution of 4-methoxyphenylmagnesium bromide, prepared from 4-bromoanisole (150 g 0.80 mol) and magnesium (20 g, 0.83 mol) in dry tetrahydrofuran (300 mL) is filtered, cooled to −10° C. and added cautiously to a stirred mixture of bis-(triphenylphosphine)nickel (II) chloride (1.5 g. 2.25 mmol) and 4-bromopyridine hydrochloride (65 g, 0.334 mol) in dry tetrahydrofuran (300 mL) at 10° C. under an argon atmosphere. After 50% of the Grignard reagent had been added a vigorous, exothermic reaction sets in and the temperature of the mixture is maintained between 50 and 60° C. throughout the rest of the addition by employing an ice-methanol cooling bath. When the addition is complete the mixture is stirred for 60 min at 50° C. The solvent is evaporated off under reduced pressure to yield a residue which is treated with t-butylmethylether (500 mL) and extracted with hydrochloric acid (3×300 mL of 5M). The combined extracts are washed (t-butylmethylether), basified (aqueous NaOH) and extracted with t-butylmethylether (4×300 mL). The combined extracts are dried (Na2SO4) and the solvent is evaporated off under reduced pressure to yield the crude product which is purified by recrystallisation from t-butylmethylether-cyclohexane to give 4-(4-methoxyphenyl)pyridine as a colourless Crystalline solid, m.p. 94-96° C.

1. filtrationis filtered
2. customexothermic reaction sets in and the temperature of the mixture
3. temperatureis maintained between 50 and 60° C. throughout the rest of the addition
4. additionWhen the addition
5. customThe solvent is evaporated off under reduced pressure
6. customto yield a residue which
7. extractionextracted with hydrochloric acid (3×300 mL of 5M)
8. washThe combined extracts are washed (t-butylmethylether)
9. extractionextracted with t-butylmethylether (4×300 mL)
10. dry with materialThe combined extracts are dried (Na2SO4)
11. customthe solvent is evaporated off under reduced pressure
12. customto yield the crude product which
13. customis purified by recrystallisation from t-butylmethylether-cyclohexane

ORD record

ord-8de117ee614e4834b69b1b6f932a56c1

Source dataset

uspto-grants-2001_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06288092B1