7-broMo-3,4-dihydro-1H-isochroMene

Synthesis

GENERAL METHODS: Substituted phenylethanol (10 mmol) was used as starting material, and chloromethyl methyl ether (15 mmol) and N,N-diisopropylethylamine (20 mmol) were added in anhydrous dichloromethane (25 mL) and the reaction was stirred under nitrogen protection at room temperature for 2.5 hours. After completion of the reaction, the reaction mixture was washed with water (2 x 50 mL), dried over anhydrous sodium sulfate and subsequently concentrated under reduced pressure to remove the solvent. The crude MOM acetal obtained was dissolved in dry acetonitrile (25 mL) and slowly added to a solution of trimethylmethylsilyl trifluoromethanesulfonate (TMSOTf, 10 mmol) that had been pre-cooled to 0 °C. The reaction was continued with stirring under nitrogen protection for 3 hours. At the end of the reaction, the reaction was quenched with 1 M sodium bicarbonate solution (20 mL). The organic phase was separated, washed with saturated saline (2 × 50 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the solvent. Finally, purification by fast column chromatography (FC) gave the target product substituted isochroman.

References

[1] Journal of the American Chemical Society, 2010, vol. 132, # 12, p. 4076 - 4077
[2] Tetrahedron Letters, 2013, vol. 54, # 30, p. 3962 - 3964
[3] Tetrahedron Letters, 2014, vol. 55, # 50, p. 6821 - 6826
[4] Chemistry - A European Journal, 2014, vol. 20, # 47, p. 15325 - 15329
[5] Advanced Synthesis and Catalysis, 2016, vol. 358, # 12, p. 1880 - 1885