反应详情

To a flask (ice cooled) containing acetic acid (7.2 ml) was added potassium cyanide (1.29 mg, 36.7 mmol) in small portions (CARE: HCN may be evolved). To this was added a mixture of acetic acid (3.6 ml) and sulfuric acid (7.3 g) slowly with stirring. The ice bath was removed and a solution of 5-(2-hydroxy-2-methylpropyl)-2-methoxyphenol (6.0 mg, 30.6 mmol) in acetic acid (4 ml) was added dropwise by syringe over 15 min. The reaction mixture was stirred at rt for 24 h. The reaction mixture was poured onto ice-water and the aqueous solution neutralised with sodium Carbonate, then extracted with diethyl ether (2×) and ethyl acetate (2×) after saturation with sodium chloride. Purification by column chromatography eluting with DCM:EtOAc; 1:1 then EtOAc:MeOH; 4:1 afforded the title compound (1.72 g, 30%) as a colourless solid. mp=152-157° C. 1H NMR (270 MHz; CDCl3) 1.21 (6H, s, 2×CH3), 2.62 (2H, s, CH2), 3.91 (3H, s, OCH3), 5.69 (1H, brs, OH), 6.60 (1H, s, CH), 6.85 (1H, s, CH), 8.07 (1H, s, CH). 13C NMR (67.5 MHz; CDCl3) 28.07 (CH3), 37.96 (CH2), 54.74 (C(CH3)2), 56.04 (CH3), 110.63 (CH), 113.83 (CH), 120.88 (C), 128.02 (C), 144.86 (C), 149.47 (C), 157.19 (C). LC/MS (ES+) tr=0.97 min, m/z 205.9 (M++H). HRMS (ES+) calcd. for C12H15NO2 (M++H) 206.1176, found 206.1169.

1. temperatureTo a flask (ice cooled)
2. additionTo this was added
3. customThe ice bath was removed
4. stirringThe reaction mixture was stirred at rt for 24 h
5. additionThe reaction mixture was poured onto ice-water
6. extractionextracted with diethyl ether (2×) and ethyl acetate (2×) after saturation with sodium chloride
7. customPurification by column chromatography
8. washeluting with DCM