# US 5,700,364 A · Electrochemical oxidation

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- Number: US 5,700,364 A
- Document ID: US5700364A
- Status: Granted
- Kind: A
- Application number: 08/742,430
- Filed: 1996-10-30
- Granted: 1997-12-23
- Earliest claimed: 1996-10-30
- Assignees: Merck & Co., Inc.
- Inventors: Kai Rossen
- Web page: https://patentgrep.com/patent/US5700364A

## CPC

- C07D 263/52: condensed with carbocyclic rings or ring systems
- C07D 413/06: linked by a carbon chain containing only aliphatic carbon atoms
- C25B 3/07: Oxygen containing compounds
- C25B 3/09: Nitrogen containing compounds
- C25B 3/11: Halogen containing compounds
- C25B 3/23: Oxidation (halogenation C25B3/27)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C25B: ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR (anodic or cathodic protection C23F13/00; single-crystal growth C30B)

## Abstract

A process for synthesizing the compounds ##STR1## wherein X is halo, consists of, at a minimum, electrochemical oxidation of the allyl acetonide reactant with halide salt in an aqueous system, the desired compounds being useful as intermediates for the synthesis of inhibitors of renin or HIV protease or other proteases.

## Claims

### Claim 1

A process for synthesizing an epoxide of formula, ##STR33## comprising the steps of: (a) providing a quantity of allyl acetonide having a structure ##STR34## in aqueous mixture with between about 0.2 to about 2.0 equivalents of halide salt, and a water miscible cosolvent;
(b) subjecting said mixture to an electric current density of between about 0.01 A/cm.sup.2 and about 0.5 A/cm.sup.2 at a temperature of between about -40.degree. C. and about 100.degree. C.;
(c) to give the desired epoxide.

### Claim 2 (depends on 1)

The process of claim 1 wherein the halide salt is selected from the group consisting of NaI, NaBr, KI, KBr, Et.sub.4 NI and Et.sub.4 NBr.

### Claim 3 (depends on 1)

The process of claim 1 wherein the water miscible cosolvent is selected from the group consisting of tetrahydrofuran, acetonitrile, dimethylformamide and N-methylpyrollidinone, and mixtures thereof.

### Claim 4 (depends on 6)

The process of claim 6 wherein the water immiscible solvent is selected from the group consisting of ethyl acetate, isopropyl acetate, related esters, toluene, methylene chloride and related halogenated solvents.

### Claim 5 (depends on 1)

The process of claim 1 wherein step (b) is carried out at a current density of about 0.1 A/cm.sup.2, in an undivided flow cell, at a temperature range between about 0.degree. C. and about 35.degree. C., for a time period to complete the reaction of between about 1 hour and about 10 hours.

### Claim 6

A process for synthesizing a halohydrin of formula, ##STR35## wherein X is halo; comprising the steps of:
(a) providing a quantity of allyl acetonide having a structure ##STR36## in aqueous mixture with between about 0.2 to about 2.0 equivalents of halide salt, and a water immiscible solvent;
(b) subjecting said mixture to an electric current density of between about 0.01 A/cm.sup.2 and about 0.5 A/cm.sup.2 at a temperature of between about -40.degree. C. and about 100.degree. C.;
(c) to give the desired halohydrin.

### Claim 7 (depends on 6)

The process of claim 6 wherein halo is either iodide or bromide.

### Claim 8 (depends on 7)

The process of claim 7 wherein the halide salt is selected from the group consisting of NaI, NaBr, KI, KBr, Et.sub.4 NI and Et.sub.4 NBr.

### Claim 9 (depends on 7)

The process of claim 7 wherein the water immiscible solvent is selected from the group consisting of ethyl acetate, isopropyl acetate, related esters, toluene, methylene chloride and related halogenated solvents.

### Claim 10 (depends on 7)

The process of claim 7 wherein step (b) is carried out at a current density of about 0.1 A/cm.sup.2, in an undivided flow cell, at a temperature range between about 0.degree. C. and about 35.degree. C., for a time period to complete the reaction of between about 1 hour and about 10 hours.

### Claim 11 (depends on 6)

The process of claim 6 wherein the halide salt is selected from the group consisting of NaI, NaBr, KI, KBr, Et.sub.4 NI and Et.sub.4 NBr.

### Claim 12 (depends on 6)

The process of claim 6 wherein step (b) is carded out at a current density of about 0.1 A/cm.sup.2, in an undivided flow cell, at a temperature range between about 0.degree. C. and about 35.degree. C., for a time period to complete the reaction of between about 1 hour and about 10 hours.

### Claim 13

A process for synthesizing an epoxide of formula, ##STR37## comprising the steps of: (a) providing one equivalent of allyl acetonide having a structure ##STR38## in aqueous suspension with between about 0.2 equivalents and about 2.5 equivalents of NaBr in a mixture of acetonitrile in water;
(b) subjecting said suspension to an electric current density of about 0.1 A/cm.sup.2, in an undivided flow cell, at a temperature of about 20.degree. C., for between about 1 hour and about 10 hours;
(c) to give the desired epoxide.

### Claim 14

A process for synthesizing a halohydrin of formula, ##STR39## wherein X is chloro or bromo; comprising the steps of:
(a) providing one equivalent of allyl acetonide having a structure ##STR40## in a biphasic system containing between about 0.2 equivalents and about 2.5 equivalents of NaI or NaBr in ethyl acetate or isopropyl acetate;
(b) subjecting said biphasic system to an electric current density of about 0.1 A/cm.sup.2, in an tin divided flow cell, at a temperature of about 20.degree. C., for between about 1 hour and about 10 hours;
(c) to give the desired halohydrin.