反应详情

180 mg (0.36 mmol) of hydrochloride obtained in Step 1 are dissolved in a mixture of 10 mL of methanol and 5 mL of dichloromethane. To the resulting solution there are added 0.04 mL (0.54 mmol, 1.5 equivalents) of formaldehyde (37% in water) and a grain of bromocresol green. 1N aqueous hydrochloric acid solution is added until the pH is 4 (yellow-coloured solution) and then stirring is carried out at 25° C. for 30 minutes. There are then added 23 mg (0.36 mmol) of sodium cyanoborohydride, stirring is carried out at 25° C. for 12 hours whilst maintaining the pH at 4, and then evaporation to dryness is carried out. There are obtained 250 mg of an oil which is purified by flash chromatography on 100 g of silica (eluant=dichloromethane/ethanol/NH4OH: 90/10/1) to yield 100 mg of the title product in the form of a colourless oil which crystallises at ambient temperature.

1. stirringstirring
2. waitis carried out at 25° C. for 12 hours
3. temperaturewhilst maintaining the pH at 4
4. customevaporation to dryness