# US 5,352,787 A · Process for the preparation of 5-(trifluoromethyl)-uracil, and the novel compounds 2,4-dichloro-5-trichloromethyl-pyrimidine and 2,4-difluoro-5-trifluoromethyl-pyrimidine

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- Number: US 5,352,787 A
- Document ID: US5352787A
- Status: Granted
- Kind: A
- Application number: 08/086,696
- Filed: 1993-07-02
- Granted: 1994-10-04
- Earliest claimed: 1992-07-09
- Assignees: Bayer Aktiengesellschaft
- Inventors: Peter Andres; Albrecht Marhold
- Web page: https://patentgrep.com/patent/US5352787A

## CPC

- C07D 239/54: as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
- C07D 239/30: Halogen atoms or nitro radicals
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

5-Trifluoromethyl-uracil is obtained by chlorinating thymine under mild conditions, further chlorinating the resulting 2,4-dichloro-5-methyl-pyrimidine under drastic conditions to give 2,4-dichloro-5-trichloromethylpyrimidine, reacting the latter with a fluorinating agent to give 2,4-fluorinated and/or -chlorinated 5- trifluoromethylpyrimidines and subjecting these to hydrolysis. The novel chemical compounds 2,4-dichloro- 5-trichloromethylpyrimidine and 2,4-difluoro-5-trifluoromethylpyrimidine are obtained in the course of this process.

## Claims

### Claim 1

A process for the preparation of 5-(trifluoromethyl)uracil, comprising:
a. chlorinating thymine by reacting thymine with phosphorus oxychloride in the presence of a tertiary amine at 20.degree. to 120.degree. C. to yield 2,4-dichloro-5-methylpyrimidine,
b. chlorinating 2,4-dichloro-5-methylpyrimidine by reacting 2,4-dichloro-5-methylpyrimidine with elemental chlorine or sulphuryl chloride at temperatures of 180.degree. to 250.degree. C., in the presence of radical-forming agents, without using a solvent, and optionally under UV irradiation to yield 2,4-dichloro-5-trichloromethylpyrimidines,
c. reacting 2,4-dichloro-5-trichloromethylpyrimidine with a catalytic amount of antimony halides and excess hydrogen fluoride or hydrogen fluoride alone to yield 2,4-fluorinated and/or chlorinated 5-trifluoromethylpyrimidine, and
d. hydrolyzing the 2,4-fluorinated and/or chlorinated 5-trifluoromethylpyrimidines with excess water and in the presence of a fluoride selected from the group consisting of potassium fluoride and sodium fluoride to yield 5-(trifluoromethyl) uracil.

### Claim 2 (depends on 1)

The process of claim 1, in which in step c) the fluorination is carried out at 80.degree. to 180.degree. C. with mixtures of antimony trifluoride and antimony pentachloride.

### Claim 3 (depends on 1)

The process of claim 1, in which in step c) the fluorination is carried out at 80.degree. to 180.degree. C. with hydrogen fluoride.

### Claim 4 (depends on 1)

The process of claim 1, in which step d) is carried out at 20.degree. to 90.degree. C.

### Claim 5

The compound 2,4-dichloro-5-trichloromethyl-pyrimidine.

### Claim 6

The compound 2,4-difluoro-5-trifluoromethyl-pyrimidine.