(4S)-4-[(4-hydrazinylphenyl)methyl]-1,3-oxazolidin-2-one

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (100 gms) and concentrated hydrochloric acid (250 ml) in water (500 ml) was treated with an 50% aqueous solution of sodium nitrite (46 gms) at −5 to 10° C. Upon completion of the reaction, as monitored by TLC, the reaction mass was further treated with stannous chloride dihydrate (420 gms) dissolved in concentrated hydrochloric acid (500 ml) and water (544 ml) at −15 to 10° C. When the reaction was complete, as monitored by HPLC, the pH of the reaction mass was adjusted in the range of 2.0 to 6.0 by adding aqueous sodium hydroxide solution. The reaction mass was cooled and filtered to separate the solid. The aqueous layer was extracted with dichloromethane and further made alkaline in the pH range of 6.0 to 10.0 with aqueous sodium hydroxide. The mixture was cooled and filtered to give solid (S)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one (III), which was then suspended in isopropanol (420 ml) and converted to the hydrochloride salt by treatment with hydrogen chloride at reflux temperature to yield the hydrochloride salt of (S)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one (IIIa). Upon completion of the reaction at −15 to 10° C The reaction mass was cooled filtered to separate the solid The aqueous layer was extracted with dichloromethane and further made alkaline in the pH range of 6.0 to 10.0 with aqueous sodium hydroxide The mixture was cooled filtered

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In an embodiment, (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one of formula (II), which was prepared using prior art methods was treated with an aqueous solution of sodium nitrite in concentrated hydrochloric acid at −5 to 10° C. After completion of reaction based on HPLC, the resulting diazonium salt was treated with stannous chloride in hydrochloric acid at −15 to 10° C. to give (S)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one of formula (III). After completion of reaction

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Zolmitriptan was first disclosed in U.S. Pat. No. 5,466,699 and the synthetic route comprises diazotization of (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one with sodium nitrite in presence of hydrochloric acid, followed by treatment of the diazonium salt with stannous chloride to give (S)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one. Further reaction of the hydrazine derivative with dimethylamino butyraldehyde diethyl acetal followed by chromatographic purification gave Zolmitriptan (I) as oil, which upon further crystallization from isopropanol gave Zolmitriptan of desired purity. (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one, in turn, was obtained from L-4-nitrophenyl alanine by treating it with thionyl chloride and methanol to give (S)-methyl-4-nitrophenyl alanate, which on reduction with sodium borohydride gave the corresponding alcohol. Further reaction of the said alcohol with phosgene in presence of potassium hydroxide followed by hydrogenation in presence of palladium on carbon gave the desired (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one.