# US 4,399,294 A · Process for the preparation of a furan derivative

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- Number: US 4,399,294 A
- Document ID: US4399294A
- Status: Granted
- Kind: A
- Application number: 06/335,686
- Filed: 1981-12-30
- Granted: 1983-08-16
- Earliest claimed: 1980-12-30
- Assignees: Glaxo Group Limited
- Inventors: David E. Bays; John W. Clitherow; Duncan B. Judd
- Web page: https://patentgrep.com/patent/US4399294A

## CPC

- C07D 405/14: containing three or more hetero rings
- C07D 307/46: Doubly bound oxygen atoms, or two oxygen atoms singly bound to the same carbon atom
- C07D 307/52: Radicals substituted by nitrogen atoms not forming part of a nitro radical
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Ranitidine is prepared by treating an aldehyde of formula (II) ##STR1## with dimethylamine and a reducing agent which is capable of effecting reductive alkylation to introduce the group Me.sub.2 NCH.sub.2 -- but which does not reduce the nitroethene group. The reaction is carried out in a suitable solvent, preferably in the presence of an acid or followed by treatment with an acid. Suitable reducing agents include, diborane, aluminium hydride and alkali or alkaline earth metal borohydrides. The aldehyde (II) may be generated in situ from an acetal of formula (III) ##STR2## where R.sub.1 and R.sub.2 are both alkyl groups or R.sub.1 OCHOR.sub.2 forms a cyclic acetal.

## Claims

### Claim 1

A process for the preparation of ranitidine of formula (I) ##STR10## which comprises treating an aldehyde of formula (II) ##STR11## with dimethylamine and a reducing agent which is capable of effecting reductive alkylation to introduce the dimethylaminomethyl group but which does not reduce the nitroethene group, the reaction being carried out in a suitable solvent.

### Claim 2 (depends on 1)

A process as claimed in claim 1 wherein said solvent is selected from the group consisting of aqueous alkanols, aqueous dioxan and aqueous tetrahydrofuran.

### Claim 3 (depends on 1)

A process as claimed in claim 1, wherein said reducing agent is selected from the group consisting of diborane, aluminium hydride and alkali and alkaline earth metal borohydrides.

### Claim 4 (depends on 3)

A process as claimed in claim 3 wherein said reducing agent is sodium borohydride or sodium cyanoborohydride.

### Claim 5 (depends on 4)

A process as claimed in claim 4 wherein reduction is effected in the presence of an acid or the reaction with the reducing agent is followed by treatment with an acid.

### Claim 6 (depends on 1)

A process as claimed in claim 1 carried out at a temperature of from 10.degree. to 100.degree. C.

### Claim 7 (depends on 1)

A process as claimed in claim 1, wherein said aldehyde of formula (II) is generated in situ from an acetal of formula (III) ##STR12## in which R.sub.1 and R.sub.2 are both alkyl groups or the group R.sub.1 OCHOR.sub.2 forms a cyclic acetal.

### Claim 8 (depends on 7)

A process as claimed in claim 7, wherein an acetal of formula (III) in which the group R.sub.1 OCHOR.sub.2 is a 1,3-dioxolan-2-yl group is hydrolysed using an inorganic or an organic acid to form said aldehyde of formula (II) in the presence of an excess of dimethylamine hydrochloride.

### Claim 9 (depends on 1)

A process as claimed in claim 1 in which said compound of formula (I) is converted into an acid addition salt.

### Claim 10 (depends on 9)

A process as claimed in claim 9 in which said acid addition salt is the hydrochloride.