GALANTAMINE PATENT

Galantamine for MemoryWhat would you think of a small, white flower that contained an exotic but very safe - and obviously natural - substance that could enable you to experience improved memory and muscle function, to counteract jet lag, to combat fatigue, and even, perhaps, to overcome impotence? Nicotine is an alkaloid that, in tiny amounts, is known to have a positive effect on cognitive functions such as learning and memory. (No, we are not recommending that you take up smoking - quite the contrary, as smoking is extremely destructive of good health.) Although you probably don't smoke, you do get nicotine in very small amounts from such foods as eggplant, potatoes, and tomatoes.Process for making galantamine - Patent - novel process for the preparation of N-methyl-N--5-hydroxy-4-methoxy benzene carboxamide which is useful as an A novel process for the preparation of N-methyl-N-(2-[4-hydroxyphenyl]ethyl)-5-hydroxy-4-methoxy benzene carboxamide, which is useful as an intermediate in the synthesis of (-)-galantamine, comprises the reaction of a 5-hydroxy-4-methoxy benzoic acid derivative with N-methyl-N-(2-[4-hydroxyphenyl]ethyl)amine. A process for the preparation of a compound of Formula I:wherein Z is a blocking group,comprising:(1) activating a compound of the Formula II:wherein Z is defined as above,with a coupling agent to give an activated compound of the Formula III:wherein X is a leaving group resulting from the use of the coupling agent; and(2) coupling the activated compound of Formula III with a compound N-methyl-N-(2-[4-hydroxyphenyl]ethyl) amine (A12) of formula:or acid salt of compound A12 to give compound of the Formula I: 1000 mL of IPA was placed in a 3 L flask and cooled to 0° C. A steady stream of methylamine gas from a cylinder was slowly passed through the IPA until the total volume reached 1750 ml. 100 g of (2-[4-hydroxyphenyl]ethyl) bromide (A11) was added to the cooled methylamine IPA solution in several portions.