# US 5,710,293 A · Method of preparation of ester derivatives of steroids

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- Number: US 5,710,293 A
- Document ID: US5710293A
- Status: Granted
- Kind: A
- Application number: 08/542,664
- Filed: 1995-10-13
- Granted: 1998-01-20
- Earliest claimed: 1995-10-13
- Assignees: The Population Council, Center for Biomedical Research
- Inventors: Fang Li
- Web page: https://patentgrep.com/patent/US5710293A

## CPC

- C07J 7/0055: {by a saturated or unsaturated hydrocarbon group}
- C07J: STEROIDS (seco-steroids C07C)

## Abstract

The present invention relates to a method of using a perchloric acid catalyzed reaction to make acyl derivatives of norprogesterone compounds and, in particular, 16-methylene-17.alpha.-hydroxy-19-norpregn-4-ene-3,20-dione.

## Claims

### Claim 1

A method of synthesizing acylated derivative of norprogesterone compounds comprising the steps of:
providing a norprogesterone compound having the tetracyclic ring system of asteroid substituted in the 16th position with an exomethylene group and having a hydroxyl group in the 17.alpha. position;
and reacting said norprogesterone compound with at least one acylating agent in the presence of perchloric acid, so as to form a reaction mixture containing the corresponding ester derivative of said norprogesterone compound.

### Claim 2 (depends on 1)

The compound produced by the method of claim 1.

### Claim 3 (depends on 1)

The method of claim 1 wherein said norprogesterone compound provided is a 16-methylene-17.alpha.-hydroxy-19-norpregn-4-ene-3,20-dione.

### Claim 4 (depends on 3)

The compound produced by the method of claim 3.

### Claim 5 (depends on 1)

The method of claim 1 wherein said acylating compound is provided in at least about a stoichiometric amount relative to the amount of said norprogesterone compound.

### Claim 6 (depends on 5)

The method of claim 5 wherein said acylating compound is provided in an amount in excess of a stoichiometric amount relative to the amount of said norprogesterone compound.

### Claim 7 (depends on 6)

The method of claim 6 wherein said acylating compound is provided in an amount of between about 1 and about 1.2 times the stoichiometric amount said norprogesterone compound.

### Claim 8 (depends on 1)

The method of claim 1 wherein said reaction is run in a solvent.

### Claim 9 (depends on 8)

The method of claim 8 wherein said solvent is selected from the group consisting of methylene chloride, benzene, toluene, chloroform, and ether.

### Claim 10 (depends on 1)

The method of claim 1 wherein said perchloric acid is provided in between about 0.1 and about 5 times the stoichiometric amount of said norprogesterone compound.

### Claim 11 (depends on 1)

The method of claim 1 wherein said acylating compound is selected from the group consisting of anhydrides, and acyl halides.

### Claim 12 (depends on 1)

The method of claim 1 wherein said reacting step is conducted at room temperature of between about 60.degree. F. and about 85.degree. F.

### Claim 13 (depends on 1)

The method of claim 1 further comprising the step of extracting said acyl derivative of said norprogesterone compound from said reaction mixture.

### Claim 14 (depends on 13)

The method of claim 13 further comprising the step of washing said acyl derivative of said norprogesterone compound.

### Claim 15 (depends on 14)

The method of claim 14 further comprising the step of drying the washed and extracted reaction product.

### Claim 16

A method of synthesizing acylated derivatives of 16-methylene-17.alpha.-hydroxy-19-norpregn-4-ene-3,20-dione comprising the steps of:
providing , a 16-methylene-17.alpha.-hydroxy-19-norpregn-4-ene-3,20-dione; and
reacting said 16-methylene-17.alpha.-hydroxy-19-norpregn-4-ene-3,20-dione with at least a stoichiometric amount of at least one acylating compound selected from the group consisting an anhydride and an acyl halide in the presence of perchloric acid at room temperature so as to form the corresponding acyl derivative thereof.

### Claim 17 (depends on 16)

The compound produced by the method of claim 16.

### Claim 18 (depends on 16)

The method of claim 16 wherein said acylating compound is an anhydride of acids of having between about 1 and about 7 carbons in length.

### Claim 19 (depends on 18)

The method of claim 18 wherein said acylating compound is selective from the group consisting of acetic anhydride, propionyl anhydride, butyric anhydride, pentanoic anhydride, hexanoic anhydride and heptanoic anhydride.

### Claim 20 (depends on 19)

The compound produced by the method of claim 19.

### Claim 21 (depends on 16)

The method of claim 16 wherein said acylating compound is an acyl halide having between about 1 and about 7 carbons in length.

### Claim 22 (depends on 21)

The method of claim 21 wherein said acyl halide is an acyl chloride.