US 12,565,482 B2 · Tedizolid intermediate and efficient preparation method thereof

Abstract

The efficient preparation method of a tedizolid intermediate includes the following steps: 1) subjecting 2-fluoro-4-substituted phenylacetic acid to a reaction with a Vilsmeier reagent, and adding a resulting reaction solution to an MX aqueous solution for quenching to obtain an intermediate shown in formula (II); and 2) subjecting the intermediate shown in formula (II) obtained in step 1) and 1-(2-methyl-2H-tetrazol-5-yl)ethanone to one-pot synthesis in the presence of an alkali and an ammonia source to obtain the intermediate shown in formula (I). In this method, a pyridine ring of the key intermediate shown in formula (I) is obtained through a ring-closing reaction of the 1-(2-methyl-2H-tetrazol-5-yl)ethanone and a Vinamidinium salt, and a key methyltetrazolyl group is introduced into the structure, which successfully avoids the use of highly-toxic sodium cyanide and sodium azide, the use of expensive palladium catalyst, and the use of methylation with low selectivity.

Claims14

Dependent claims

A method of preparing a tedizolid intermediate of formula (I):

wherein R1 is selected from the group consisting of:
nitro, benzyloxycarbonylamino, chlorine, bromine, iodine, trifluorosulfonyloxy, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy, and carboxylate;
the method comprising the following steps:
1) Subjecting 2-fluoro-4-substituted phenylacetic acid to a reaction with a Vilsmeier reagent, and adding a resulting reaction solution to an MX aqueous solution for quenching to obtain an intermediate shown in formula (II):
wherein the MX is selected from the group consisting of:
sodium tetrafluoroborate, potassium tetrafluoroborate, sodium perchlorate, sodium hexafluorophosphate, and potassium hexafluorophosphate, and
x⊖ is selected from the group consisting of:
a tetrafluoroborate ion, a perchlorate ion, and a hexafluorophosphate ion;
and
2) subjecting the intermediate shown in formula (II) obtained in step 1) and 1-(2-methyl-2H-tetrazol-5-yl) ethanone to a one-pot synthesis in the presence of an alkali and an ammonia source to obtain the tedizolid intermediate shown in formula (I):

7 more elements

Dependencies are inferred from the claim text.

Tedizolid intermediate and efficient preparation method thereof

Life of this patent

Tedizolid intermediate and efficient preparation method thereof

Life of this patent

Abstract

Claims14