Methyl thiocyanate → 7-Hydroxy-chroman-6-carbonitrile

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Reaction Steps

In a 250 mL round-bottom flask was placed Chroman-7-ol (1.8 g, 12.0 mmol, from Step 3-1-2) in dry dichloroethane (30 mL ) under argon. The solution was cooled to 0° C. where boron trichloride (13.2 mL, 1M in CH2Cl2, 13.2 mmol, 1.1 eq) was added dropwise. At this point, methyl thiocyanate (0.97 g, 13.2 mmol, 1.1 eq) was added followed by aluminum trichloride (1.6 g, 12.0 mmol, 1 eq). The reaction was allowed to warm up to rt and stirred for 17 h. The reaction mixture was cooled down to 0° C. and 10 mL of 50% w/w NaOH was added to adjust the solution to PH˜14, followed by 40 mL of water. The solution was then refluxed at 65° C. for 2 h. The solution was allowed to cool to ambient temperature. The aqueous layer was washed with dichloromethane (20 mL). The aqueous solution was then transferred to an Erlenmeyer flask and acidified to pH˜1 with conc. HCl (aq.). This solution was extracted with EtOAc (3×20 mL) and the combined organic layers were dried over Na2SO4, filtered and evaporated. The residue was suspended in cold CH2Cl2 and filtered. The filtrate was concentrated and the suspension procedure was repeated until no further solid precipitated. The combined solids were found to be nearly pure product with minor contaminants. The desired product was white solid (1.20 g, 54.3%). 1H-NMR (CD3CN) δ 7.87 (s, 1H, OH), 7.25 (s, 1H), 6.35 (s, 1H), 4.21 (t, 2H), 2.70 (t, 2H), 1.98 (m, 2H).

Provenance & Evidence