Phosphorus tribromide → 1-Bromo-2-(3-methoxyphenyl)ethane

To a cold solution of 3-methoxyphenethyl alcohol (7.55 g, 50 mmol) in 20 ml of dry (sieves) methylene chloride, a solution of phosphorus tribromide (7 g, 26 mmol) in 20 ml of methylene chloride was slowly added under nitrogen. The reaction mixture was permitted to warm to ambient temperature overnight. The reaction was then quenched in ice/water slowly and the resulting solution neutralized with 5N NaOH and then extracted with methylene chloride. The combined extracts were washed with water and brine, dried with anhydrous magnesium sulfate and concentrated to give 7.3 g of 3-methoxyphenethyl bromide. A solution of this bromide (7.3 g) in 10 ml of dry tetrahydrofuran (THF) was slowly added to a flask containing magnesium chips (1.03 g) and a small crystal of iodine in 30 ml of THF. The reaction mixture was then heated to reflux for 1 hour. To this mixture which was cooled with ice, a solution of dry acetone (2.2 g) in 10 ml of dry THF was added and the reaction mixture stirred at ambient temperature overnight. The mixture was quenched (0° C.) with a cold solution of NH4Cl followed by 1N HCl. The mixture was extracted with ethyl acetate and dried with anhydrous magnesium sulfate. Concentration and chromatography on silica gel (10-30% ethyl acetate in hexanes) afforded 2.31 g of carbinol. This carbinol (2.3 g) in 4 ml of glacial acetic acid was slowly added to a solution of KCN (2.36 g) and H2SO4 (3.63 g) in 15 ml of acetic acid. The reaction mixture was then stirred at 90° C. (bath temperature) overnight under nitrogen. Additional KCN (3.28 g), H2SO4 (8 ml in 24 ml of acetic acid) and acetic acid (18 ml) were added and the reaction mixture heated overnight. The reaction was quenched by pouring the reaction mixture into ice/water and adjusting the pH of the solution to neutrality with 5N NaOH. The solution was repeatedly extracted with ethyl acetate and the combined extracts backwashed with water and brine and then dried with anhydrous sodium sulfate. Concentration afforded 1.64 g of formamide which was hydrolyzed to the amine in 6N HCl (40 ml) at reflux for 3 hours. The reaction mixture was partially concentrated, diluted with water and the pH of the solution adjusted with 5N NaOH to 12. The solution was extracted with ethyl acetate and the combined extracts backwashed with brine and dried with anhydrous sodium sulfate. Concentration gave 1.2 g of the titled amine.

1. customThe reaction was then quenched in ice/water slowly
2. extractionextracted with methylene chloride
3. washThe combined extracts were washed with water and brine
4. dry with materialdried with anhydrous magnesium sulfate
5. concentrationconcentrated

ORD record

ord-46c0d5c0906c49439953d5c5b6ac6ded

Source dataset

uspto-grants-1990_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04906645