# US 5,688,954 A · Process for the preparation of substituted thiopyran-1-oxides

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- Number: US 5,688,954 A
- Document ID: US5688954A
- Status: Granted
- Kind: A
- Application number: 08/633,749
- Filed: 1996-04-24
- Granted: 1997-11-18
- Earliest claimed: 1993-10-25
- Assignees: Rhone-Poulenc Rorer S.A.
- Inventors: Philippe Pitchen; Matthew Powers; Patrick Leon; Dominique Petre
- Web page: https://patentgrep.com/patent/US5688954A

## CPC

- C07D 409/04: directly linked by a ring-member-to-ring-member bond
- A61P 9/12: Antihypertensives
- C07D 213/32: Sulfur atoms
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A process is described for the preparation of a compound of formula (IX) from 4-hydroxybutyl 3-pyridyl ketone. The compound of formula (IX) is an intermediate useful in the preparation of (1R,2R)-2-(3-pyridyl)-N-alkyl-tetrahydro-2H-thiopyran-2-carbothioamide 1-oxides which possess useful pharmaceutical properties, for example anti-hypertensive properties. ##STR1##

## Claims

### Claim 1

A process for the preparation of a compound of formula (IX) ##STR3## which comprises the following step sequence: a) reducing a compound of formula (XI) ##STR4## wherein R.sup.2 is a straight or branched C.sub.1-4 alkyl group or a salt or addition compound thereof using a chiral reducing agent or by biochemical reducing means to provide a compound of formula (X) ##STR5## wherein R.sup.2 is as defined previously; b) converting a compound of formula (X) to a compound of formula (XII) ##STR6## wherein R.sup.2 is as defined previously and R.sup.3 represents an alkyl- or arylsulphonyl group; and
c) cyclising the so-formed (R) isomer of formula (XII) to provide the desired (S) isomer of formula (IX).

### Claim 2

A process for the preparation of a compound of formula (IX) ##STR7## which comprises cyclising a compound of formula (XII) ##STR8## wherein R.sup.2 represents a straight or branched C.sub.1-4 alkyl group and R.sup.3 is an alkyl or arylsulphonyl group.

### Claim 3

A process for the preparation of a compound of formula (X) ##STR9## wherein R.sup.2 represents a straight or branched C.sub.1-4 alkyl group, which comprises reducing a compound of formula (XI) ##STR10## wherein R.sup.2 is as defined previously, or a salt or addition compound thereof using a chiral reducing agent or by biochemical reducing means.

### Claim 4 (depends on 1)

A process as claimed in claim 1 wherein a compound of formula (XII) is cyclised by treatment with a nucleophilic base.

### Claim 5 (depends on 4)

A process as claimed in claim 4 wherein the nucleophilic base is an alkali metal alkoxide and the reaction is effected in an alkanol solvent.

### Claim 6 (depends on 1)

A process as claimed in claim 1 wherein the reduction to provide a compound of formula (X) is effected chemically using an asymmetric borane derivative.

### Claim 7 (depends on 6)

A process as claimed in claim 6 wherein the reduction is effected at a temperature of about -10.degree. C. to about -20.degree. C.

### Claim 8 (depends on 1)

A process as claimed in claim 1 wherein the reduction to provide a compound of formula (X) is effected biochemically using a culture of the microorganism Hansenulla Polymorpha.

### Claim 9

A compound of formula (X) ##STR11## wherein R.sup.2 is a straight or branched C.sub.1-4 alkyl group, and salts thereof.

### Claim 10

A compound of formula (XII) ##STR12## wherein R.sup.2 is a straight or branched C.sub.1-4 alkyl group and R.sup.3 is alkyl-or arylsulphonyl, and salts thereof.

### Claim 11 (depends on 3)

A process as claimed in claim 3 wherein the reduction to provide a compound of formula (X) is effected biochemically using a culture of the microorganism Hansenulla Polymorpha.