# US 5,688,983 A · Process for the preparation of tetraethyl methylenebisphosphonate

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- Number: US 5,688,983 A
- Document ID: US5688983A
- Status: Granted
- Kind: A
- Application number: 08/614,234
- Filed: 1996-03-12
- Granted: 1997-11-18
- Earliest claimed: 1996-03-12
- Assignees: Zeneca Limited
- Inventors: Michael R. Leadbetter; Richard W. Brown; Maureen M. McKenna
- Web page: https://patentgrep.com/patent/US5688983A

## CPC

- C07F 9/4028: {containing no further substituents than -PO3H2 groups in free or esterified form}
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

This invention relates to a process for the preparation of tetraethyl methylenebisphosphonate by the reaction of dichloromethane with diethyl phosphite, wherein the reaction is performed in a polar aprotic solvent or mixtures thereof.

## Claims

### Claim 1

A process for preparing a compound of formula (I) ##STR5## comprising: reacting a compound of the formula (II) ##STR6## wherein M is selected from the group consisting of alkali metals, alkaline earth metals and hydrogen, with dichloromethane in the presence of at least one polar aprotic solvent other than dichloromethane.

### Claim 2 (depends on 1)

A process according to claim 1, wherein the base is selected from the group consisting of sodium hydride, potassium hydride and sodium ethoxide.

### Claim 3 (depends on 1)

A process according to claim 1, wherein the polar aprotic solvent is selected from the group consisting of N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, N-methyl-pyrrolidinone, acetonitrile and mixtures thereof.

### Claim 4 (depends on 1)

A process according to claim 1, wherein M is an alkali metal.

### Claim 5 (depends on 4)

A process according to claim 4, wherein M is an alkali metal selected from the group consisting of lithium, sodium and potassium.

### Claim 6 (depends on 1)

A process according to claim 1, wherein M is an alkaline earth metal.

### Claim 7 (depends on 6)

A process according to claim 6, wherein M is an alkaline earth metal selected from the group consisting of calcium, magnesium and barium.

### Claim 8 (depends on 1)

A process according to claim 1, wherein the amount of polar aprotic solvent to moles of diethyl phosphite is 100 mL to 1 mole.

### Claim 9 (depends on 3)

A process according to claim 3, wherein the polar aprotic solvent is dimethyl sulfoxide.

### Claim 10 (depends on 3)

A process according to claim 3, wherein the polar aprotic solvent is N,N-dimethylformamide.

### Claim 11 (depends on 1)

A process according to claim 1, wherein the ratio of dichloromethane to a compound of formula II is between 1:2 to 1:1.

### Claim 12 (depends on 1)

A process according to claim 1, wherein the ratio of dichloromethane to a compound of formula II is 1:2.

### Claim 13

A process for preparing a compound of formula (I) ##STR7## comprising the steps of: a) reacting diethylphosphite with a base to form a compound of formula (II) ##STR8## wherein M is selected from the group consisting of an alkali metal, an alkaline earth metal and hydrogen; and
b) reacting dichloromethane with said compound of formula II in the presence of a polar aprotic solvent or mixtures thereof other than dichloromethane.