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(2,3-Dimethoxyphenyl)oxirane
A mixture of powdered sodium hydride 60% in mineral oil (2.0 g, 0.05 mol) was
washed with hexane and then suspended in anhydrous DMSO (40.0 mL) and stirred
under nitrogen at 75°C until evolution of hydrogen ceased (ca. 0.5 h). The
solution was cooled to room temperature, diluted with anhydrous THF (40 mL),
and then cooled to -5°C with an ice-salt bath. A solution of
trimethylsulfonium iodide (10.2 g, 0.05 mol) in anhydrous DMSO (40 mL) was
added to the resulting mixture over the course of about 3 min and without
stirring. After completion of the addition, the reaction mixture was stirred
for 1 min and then treated dropwise with a solution of
2,3-dimethoxybenzaldehyde (6.9 g, 0.041 mol) in anhydrous DMSO (100 mL). The
mixture was stirred at the same temperature for 15 min and at room
temperature for 12 h and was then poured into H20 and extracted with ethyl
acetate. Evaporation of the washed (H2O) and dried extracts yielded an oil
consisting of (2,3-dimethoxyphenyl)oxirane (6.0 g, 81%) which was directly
used in the subsequent transformation.
2-(2,3-Dimethoxyphenyl)ethanol
A stirred solution of NaBH4 (1.06 g, 28.02 mmol) in anhydrous THF (7.5 mL)
was cooled in an ice bath under nitrogen and then treated with a solution of
BF3*Et2O (3.45 mL, 28.02 mmol) in anhydrous THF (8.5 mL). The resulting
mixture was diluted with anhydrous THF (65 mL) and then treated in succession
with BF3*Et2O (3.45 mL, 28.02 mmol) and a solution of
(2,3-dimethoxyphenyl)oxirane (5.05 g, 28.02 mmol) in anhydrous THF (28 mL).
The reaction mixture was stirred for 1 h at the same temperature and was then
hydrolyzed with water and saturated with potassium carbonate. Evaporation of
the washed (H2O) and dried organic layer yielded an oil which was purified by
distillation to afford 2-(2,3-Dimethoxyphenyl)ethanol (2.0 g, 40%): bp
93-95°C/0.6mmHg.
Ref: Journal of Medicinal Chemistry, 1993, Vol. 36, No. 21, pp 3077-3086
The
idea here is then to make the mesylate/tosylate of the alcohol and substitute
it with azide for further reduction (Mg, Ca or NaBH4) to the phenetylamine,
alternatively make the azide (or a protected amine) directly using Mitsunobu
conditions.
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