Deprotection Procedure for the Nosyl Protecting Group:
A 100mL, two-necked, round-bottom flask equipped with a magnetic stirring bar, nitrogen gas inlet, and a rubber septum is charged with 75 mmol of Thiophenol (7.5 mL) and 20 mL of acetonitrile. The mixture is cooled in an ice-water bath and 75 mmol of 10 M aqueous KOH solution (7 mL) is added over a period of 10 min. After 5 min, the ice-water bath is removed, and 30 mmol of the Nosyl-amine in 20 mL acetonitrile is added over 20 min. The reaction mixture is heated in a 50°C oil bath for 45 min and then allowed to cool down to room temperature. Dilution with 80 mL of water and extraction with three 80 mL portions of dichloromethane follows. The combined organic extracts are washed with 80 mL brine, dried over magnesium sulphate, filtered, and concentrated under reduced pressure. The residue is purified by column chromatography on silica to give the desired secondary amine and its hydrochloride salt. The residue is dissolved in 120 mL of dichloromethane and washed with two 80 mL portions of 1 M aqueous NaOH solution, 40 mL of brine, dried over magnesium sulphate, filtered and concentrated under reduced pressure. Bulb-to-bulb distillation provides normally a yield of 90% of the secondary amine.
References:
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T. Fukuyama et al., Tetr.Lett., 1995; 36: 6373
T. Wang et al., Tetr. 1998; 54: 7955
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Y. Hidai et al., Chem.Pharm.Bull. 2000; 48: 1570
T. Kan et al., Synlett. 2002; 1338
T. Kan, T. Fukuyama; Chem. Comm. 2004; 4: 353-359
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