# US 5,710,280 A · Preparation of fluconazole and pharmaceutically acceptable salts thereof

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- Number: US 5,710,280 A
- Document ID: US5710280A
- Status: Granted
- Kind: A
- Application number: 08/679,457
- Filed: 1996-07-09
- Granted: 1998-01-20
- Earliest claimed: 1996-07-09
- Assignees: Development Center for Biotechnology
- Inventors: Kae-Shyang Shih; Lie-Rong Chen; Ching-Wei Liu; Chia-Lin J. Wang
- Web page: https://patentgrep.com/patent/US5710280A

## CPC

- C07D 231/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 233/56: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D 249/08: 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

A process for preparing fluconazole, including the steps of (1) acylating 1,3-difluorobenzene (DFB) to obtain 2-chloro-2',4'-difluoroacetophenone (CAP); (2) alkylating 4-amino-4H-1,2,4-triazole (4-AT) with CAP to obtain 2-(1H-1,2,4-triazol-1-yl)-2',4'-difluoroacetophenone (TAAP) salt; (3) deaminating TAAP salt to obtain TAAP; and (4) reacting TAAP with 1,2,4-triazole to obtain fluconazole.

## Claims

### Claim 1

A process for preparing 2-(2,4-difluorophenyl)-1,3-bis-(1H-1,2,4-triazol-1-yl)propan-2-ol, said process comprising
(1) acylating 1,3-difluorobenzene (DFB) to obtain 2-chloro-2',4'-difluoroacetophenone (CAP);
(2) alkylating 4-amino-4H-1,2,4-triazole (4-AT) with CAP to obtain 2-(1H-1,2,4-triazol-1-yl)-2',4'-difluoroacetophenone (TAAP) salt;
(3) deaminating TAAP salt to obtain TAAP; and
(4) reacting TAAP with 1,2,4-triazole to obtain fluconazole.

### Claim 2 (depends on 1)

The process of claim 1, wherein said step (1) is conducted by acylating DFB with chloroacetyl halide.

### Claim 3 (depends on 1)

The process of claim 1, wherein said step (3) is conducted by deaminating TAAP salt with an acid.

### Claim 4 (depends on 2)

The process of claim 2, wherein said step (3) is conducted by deaminating TAAP salt with an acid.

### Claim 5 (depends on 2)

The process of claim 2, wherein chloroacetyl halide is chloroacetyl chloride.

### Claim 6 (depends on 3)

The process of claim 3, wherein chloroacetyl halide is chloroacetyl chloride.

### Claim 7 (depends on 4)

The process of claim 4, wherein chloroacetyl halide is chloroacetyl chloride.

### Claim 8 (depends on 1)

The process of claim 1, wherein said step (4) is conducted in an aqueous solvent which contains a strong base.

### Claim 9 (depends on 2)

The process of claim 2, wherein said step (4) is conducted in an aqueous solvent which contains a strong base.

### Claim 10 (depends on 3)

The process of claim 3, wherein said step (4) is conducted in an aqueous solvent which contains a strong base.

### Claim 11 (depends on 4)

The process of claim 4, wherein said step (4) is conducted in an aqueous solvent which contains a strong base.

### Claim 12 (depends on 5)

The process of claim 5, wherein said step (4) is conducted in an aqueous solvent which contains a strong base.

### Claim 13 (depends on 6)

The process of claim 6, wherein said step (4) is conducted in an aqueous solvent which contains a strong base.

### Claim 14 (depends on 7)

The process of claim 7, wherein said step (4) is conducted in an aqueous solvent which contains a strong base.

### Claim 15 (depends on 5)

The process of claim 5, wherein said step (1) is conducted with aluminum trichloride as the catalyst and dichloromethane as the solvent.

### Claim 16 (depends on 6)

The process of claim 6, wherein said step (1) is conducted with aluminum trichloride as the catalyst and dichloromethane as the solvent.

### Claim 17 (depends on 7)

The process of claim 7, wherein said step (1) is conducted with aluminum trichloride as the catalyst and dichloromethane as the solvent.

### Claim 18 (depends on 14)

The process of claim 14, wherein said step (1) is conducted with aluminum trichloride as the catalyst and dichloromethane as the solvent.

### Claim 19 (depends on 14)

The process of claim 14, wherein said acid used in step (3) is diluted hydrochloric acid.

### Claim 20 (depends on 14)

The process of claim 14, wherein said aqueous solvent used in step (4) is water.