# US 4,395,561 A · Synthesis of 3-hydroxyoxetane

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- Number: US 4,395,561 A
- Document ID: US4395561A
- Status: Granted
- Kind: A
- Application number: 06/378,167
- Filed: 1982-05-14
- Granted: 1983-07-26
- Earliest claimed: 1982-05-14
- Assignees: The United States of America as represented by the Secretary of the Navy
- Inventors: Kurt Baum; Vytautas Grakauskas; Phillip T. Berkowitz
- Web page: https://patentgrep.com/patent/US4395561A

## CPC

- C07D 407/12: linked by a chain containing hetero atoms as chain links
- C07D 305/08: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring atoms
- C07D 309/12: only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

A process for preparing 3-hydroxyoxetane comprising the following steps in order (1) reacting a carboxylic acid of the formula CH.sub.3 (CH.sub.2).sub.n COOH with epichlorohydrin in the presence of anhydrous ferric chloride to produce an ester of the formula ##STR1## wherein n is an integer of from 0 to 3; (2) protecting the secondary hydroxy group of the ester with a blocking group, Z, that is stable to bases; thus forming a blocked ester of the formula ##STR2## (3) hydrolyzing the blocked ester formed in step (2) with an aqueous base to remove the carboxylic acid and form a 3-hydroxyoxetane derivative of the formula ##STR3## in which Z represents the blocking group; (4) removing the blocking group from the 3-hydroxyoxetane derivative by heating it with an alcohol and an acid to form the product 3-hydroxyoxetane, ##STR4##

## Claims

### Claim 1

A process for preparing 3-hydroxyoxetane comprising the following steps in order:
(1) reacting a carboxylic acid of the formula CH.sub.3 (CH.sub.2).sub.n COOH with epichlorohydrin in the presence of a catalytic amount of anhydrous ferric chloride to produce an ester of the formula ##STR22## wherein n is an integer of from 0 to 3; (2) reacting the ester formed in step (1) with a blocking agent selected from the group consisting of
(a) dihydropyran,
(b) ethyl vinyl ether,
(c) propyl vinyl ether,
(d) n-butyl vinyl ether, and
(e) isopentyl vinyl ether
in the presence of a catalyst selected from the group consisting of pyridinium p-toluenesulfonate and toluenesulfonic acid to form a blocked ester of the formula ##STR23## wherein n is an integer of from 0 to 3 and Z is selected from the group consisting of ##STR24## (3) hydrolyzing the blocked ester formed in step (2) with an aqueous base to remove the carboxylic acid and form a 3-hydroxyoxetane derivative of the formula ##STR25## wherein Z is defined in step (2); (4) removing the blocking group from the 3-hydroxyoxetane derivative by heating it with an alcohol and an acid to form the produce 3-hydroxyoxetane, ##STR26## (5) isolating the product 3-hydroxyoxetane.

### Claim 2 (depends on 1)

The process of claim 1 wherein the carboxylic acid used in step (1) is acetic acid and the ester produced is 3-chloro-2-hydroxyl-1-propyl acetate, ##STR27##

### Claim 3 (depends on 1)

The process of claim 1 wherein the reaction temperature of step (1) is kept in the range of from about 20.degree. C. to about 100.degree. C.

### Claim 4 (depends on 1)

The process of claim 1 wherein dihydropyran is used as the blocking agent in step (2).

### Claim 5 (depends on 4)

The process of claim 4 wherein a trace amount of toluenesulfonic acid is used as the catalyst in step (2).

### Claim 6 (depends on 1)

The process of claim 1 wherein the blocking agent used in step (2) is selected from the group consisting of ethyl vinyl ether, propyl vinyl ether, n-butyl vinyl ether, and isopentyl vinyl ether.

### Claim 7 (depends on 6)

The process of claim 6 wherein the blocking agent used in step (2) is ethyl vinyl ether.

### Claim 8 (depends on 6)

The process of claim 6 wherein a trace amount of toluenesulfonic acid is used as the catalyst in step (2).

### Claim 9 (depends on 1)

The process of claim 1 wherein the based used in step (3) is NaOH.

### Claim 10 (depends on 1)

The process of claim 1 wherein the base used in step (3) is KOH.

### Claim 11 (depends on 1)

The process of claim 1 wherein the hydrolysis of step (3) is performed at reflux temperature.

### Claim 12 (depends on 1)

The process of claim 1 wherein the alcohol used in step (4) is selected from the group consisting of methanol, ethanol, 1-propanol, 2-propanol, and mixtures thereof.

### Claim 13 (depends on 12)

The process of claim 12 wherein the alcohol is methanol.

### Claim 14 (depends on 1)

The process of claim 1 wherein the acid catalyst used in step (4) is toluenesulfonic acid.

### Claim 15 (depends on 1)

The process of claim 1 wherein the acid catalyst used in step (4) is pyridinium p-toluenesulfonate.