Process for the preparation of pyridine derivatives

Details Process for the preparation of pyridine derivatives Process for the preparation of pyridine derivatives

2000-01-03

2001-11-06

Rotman, Alan L. (Department: 1625)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

active

06313303

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to a method for producing a sulfoxide which is useful as a medicament such as an inhibitor of gastric acid secretion or an anti-ulcer agent or an intermediate for producing medicaments, as described in JP-A 1-6270 (Example 32), JP-A61-50978 (Example 2), JP-A54-141783 (Example 21), JP-A61-22079 etc., in a good yield at a high purity with safety.
PRIOR ART
Conventionally, sulfoxide has been produced by oxidizing thioether with oxidants such as hydrogen peroxide, m-chloroperbenzoic acid, sodiumhypochlorite, and sodiumbromite, as described in JP-A 1-6270 (EP-268956, U.S. Pat. No. 5,045,552), JP-A 61-50978 (EP-174726, U.S. Pat. No. 4,628,098), JP-A 54-141783 (EP-5129, U.S. Pat. No. 4,255,431) or JP-A 61-22079 (EP-166287, U.S. Pat. No. 4,758,579). (See the following formula, wherein R
1
to R
4
have the same meanings as described below).
Among the above oxidants, from viewpoints of readiness in weighing, storage stability and reaction activity and the like, m-chloroperbenzoic acid is frequently used.
In Example 32 of JP-A 1-6270, for example, thioether is oxidized by using 0.96 equivalent (on a purity basis) of m-chloroperbenzoic acid, to produce sulfoxide at a yield of 80%, which is not an industrially satisfactory yield.
Depending on the reaction conditions, disadvantageously, the reaction does not ceased at the stage of sulfoxide production but further proceeds to a side reaction where a part of the produced sulfoxide is furthermore oxidized to sulfone as shown in the following reaction scheme. When sulfone is formed, there is a problem not only that the yield of the objective sulfoxide is reduced, but also that it is difficult to separate and purify them, since there is a close resemblance in physicochemical property between the two. (In the formula, R
1
to R
4
have the same meanings as described below.)
In JP-A 1-6270 and the like, additionally, the oxidation is conducted in dichloromethane (methylene chloride), but from a viewpoint of environmental strategies, there is a problem that halogenated hydrocarbon solvents can never be used industrially.
Additionally, since m-chloroperbenzoic acid is expensive, it is extremely disadvantageous from a viewpoint of the production cost. Still additionally, m-chloroperbenzoic acid is listed as a dangerous material and therefore requires deep attention for the use and storage thereof, inconveniently for large-scale handling.
As has been described above, no industrially excellent method for producing sulfoxide (II) has been established yet. Accordingly, a novel excellent method for producing sulfoxide (II) has been required.
DISCLOSURE OF THE INVENTION
The present inventors have made intensive investigations so as to solve the above-mentioned problems. As a result, they have found that the objective sulfoxide (II) can be produced in a good yield with no formation of a byproduct sulfone, safety, with no use of any halogenated hydrocarbon solvent. Thus, they have accomplished the present invention.
The present invention is a method for producing sulfoxide (II) represented by the following formula (II):
(wherein R
1
to R
4
have the same meanings as described below), which comprises the step of oxidizing thioether (I) represented by the following formula (I):
(wherein R
1
represents hydrogen atom, methoxy group or difluoromethoxy group; R
2
represents methyl group or methoxy group; R
3
represents 3-methoxypropoxy group, methoxy group or 2,2,2-trifluoroethoxy group; and R
4
represents hydrogen atom or methyl group) with a). a perborate in the presence of an acid anhydride or a metal catalyst, or b). N-halosuccinimide, 1,3-dihalo-5,5-dimethylhydantoin or dichloroisocyanurate in the presence of a base.
More specifically, thioether (I) is a compound which is identical to 2-{[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylthio}-1H-benzimidazole described in JP-A 1-6270 (Example 31), the compound described in JP-A 61-50978 (Example 1) (R
1
=H, R
2
=CH
3
, R
3
=H, R
4
=CH
2
CF
3
and n=0; chemical name: 2-{[4-(2,2,2-trifluoroethoxy)-3-methylpyridin-2-yl]methylthio}-1H-benzimidazole), 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridyl)methylthio]-1H-benzimidazole as a precursor of the compound described in JP-A 54-141783 (Example 21) or 5-difluoromethoxy-2-[(4,5-dimethoxy-2-pyridyl)methylthio]-1H-benzimidazole as a precursor of the compound described in JP-A 61-22079, and is a starting material of the present invention. All the compounds can be produced by the methods described in each publication.
More specifically, sulfoxide (II) is identical to 2-{[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl}-1H-benzimidazole (general name: Rabeprazole free base) described in JP-A 1-6270 (Example 32), the compound described in JP-A 61-50978 (Example 2) (R
1
=H, R
2
=CH
3
, R
3
=H, R
4
=CH
2
CF
3
and n=1; general name: Lansoprazole; chemical name: 2-{[4-(2,2,2-trifluoroethoxy)-3-methylpyridin-2-yl]methylsulfinyl}-1H-benzimidazole), 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridyl)methylsulfinyl]-1H-benzimidazole (general name: Omeprazole) described in JP-A 54-141783 (Example 21) or 5-difluoromethoxy-2-[(4,5-dimethoxy-2-pyridyl)methylsulfinyl]-1H-benzimidazole (general name: Pantoprazole) described in JP-A 61-22079, and is the objective compound of the present invention.
More specifically, sulfoxide (II) includes for example the following compounds:
The method of production of the present invention is now described in detail.
The present invention encompasses the embodiments a) and b) described above.
The embodiments a) and b) are described hereinafter.
The type of perborate which is an oxidant used in the embodiment a) is not limited, but generally, the sodium perborate is preferable. Further, the perborate may occasionally form a hydrate at no limited hydration quantity, and generally, tetrahydrate or monohydrate is preferable. Additionally, sodium perborate·tetrahydrate (NaBO
3
.4H
2
O; CAS Registration No. 10486-00-7) and sodium perborate·monohydrate (NaBO
3
.H
2
O; CAS Registration No. 10332-33-9) are commercially available as reagents and industrial raw materials and the like.
The amount of perborate to be used is not also limited, but generally it is used in the range of from 0.8 to 1.7 equivalents, more preferably from 0.85 to 1.6 equivalents and further preferably from 0.9 to 1.5 equivalents to thioether (I).
The type of N-halosuccinimide which is an oxidant used in the embodiment b) is not also limited, but generally, N-chlorosuccinimide (CAS Registration No. 128-09-6) or N-bromosuccinimide (CAS Registration No. 128-08-5) is preferable. Additionally, N-halosuccinimide is also commercially available as a reagent and an industrial raw material and the like.
The amount of N-halosuccinimide to be used is not also limited, but generally it is used in the range of from 0.8 to 1.7 equivalents, more preferably from 0.85 to 1.6 equivalents and further preferably from 0.9 to 1.5 equivalents to thioether (I).
Next, the type of 1,3-dihalo-5,5-dimethylhydantoin used in the embodiment b) is not also limited, but generally, 1,3-dichloro-5,5-dimethylhydantoin (CAS Registration No. 118-52-5) or 1,3-dibromo-5,5-dimethylhydantoin (CAS Registration No. 77-48-5) is preferable. Additionally, 1,3-dihalo-5,5-dimethylhydantoin is also commercially available as a reagent and an industrial raw material and the like.
The amount of 1,3-dihalo-5,5-dimethylhydantoin is not also limited, but generally it is used in the range of from 0.3 to 1.0 equivalent, more preferably from 0.35 to 0.9 equivalent, further preferably from 0.4 to 0.8 equivalent to thioether (I).
The type of dichloroisocyanurate used in the embodiment b) is not also limited, but generally, sodium dichloroisocyanurate (CAS Registration No. 2893-78-9) or potassium dichloroisocyanurate (CAS Registration No. 2244-21-5) is preferable. Furthermore, the dichloroisocyan

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