79566-22-6Relevant academic research and scientific papers
PROCESS FOR PREPARING REL-(3R*,3AS*,7AS*)-3-BENZYL-2-METHYL-2,3, 3A,4,5,6,7,7A- OCTAHYDROBENZO[D]ISOXAZOI-4-ONE OR A SALT THEREOF
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, (2011/02/24)
The invention concerns a process for preparing BTG-1640, i.e. rel- (3R*,3aS*,7aS*)-3-benzyl-2-methyl-2,3,3a,4,5,6,7,7a-octahydrobenzo[d]isoxazol- 4-one or a salt thereof, comprising the following steps: d) adding phenylacetaldehyde (4) to N-methylhydroxylamine (5) in the form of a salt in the presence of an organic base selected from the group consisting of tertiary amines NR1 R2R3, where R1, R2, R3 independently from each other represent a C1-C4 alkyl group, alkali or alkaline earth metal (C1-C4)alkoxides, alkali or alkaline earth metal (C1-C4)carboxylates, and in the presence of an anhydrous polar solvent selected from the group consisting of C1-C5 alcohols, formamide, dimethylformamide, dimethylsulphoxide, at a temperature within the range from O°C to 12O°C to provide, after removal of the solvent, a solid mixture of nitrone monomer (3) and dimer (10), wherein the nitrone to dimer ratio is within the range from 90:10 to 0:100; e) reacting the solid mixture obtained in step d), wherein the ratio of the nitrone to dimer is within the range from 90:10 to 0:100, with cyclohexenone (2); f) subjecting the crude reaction product obtained in e), having been optionally evaporated to dryness and retaken in a water-immiscible solvent, to at least one wash with water followed by evaporating the organic phase to dryness; g) separating the BTG-1640 as an oxalate salt (1c) by precipitating with oxalic acid added to the organic phase in the dry state; and h) optionally freeing the BTG-1640 base from the oxalate salt.
