Hydrochloric Acid → (S)-4-(4-hydrazinobenzyl)-2-oxazolidinone
Reaction equation
CN(CCC1[C:10]2[CH:11]=[C:12]([CH2:15][C@@H:16]3[NH:21][C:19](=[O:20])[O:18][CH2:17]3)[CH:13]=[CH:14][C:9]=2[NH:8]C=1)C.[NH2:22]C1C=CC(C[C@H]2COC(=O)N2)=CC=1.N([O-])=O.[Na+].Cl>>[NH:8]([C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C@H:16]2[CH2:17][O:18][C:19](=[O:20])[NH:21]2)=[CH:11][CH:10]=1)[NH2:22]Participants
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.
Sources & evidence
- ORD record
- ord-95155dbb31184755aedbd79a74f242d2
- Source dataset
- uspto-grants-2015_04
- Patent number
- US09006453B2
Reaction notes
Loading…