Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2001-01-17
2003-02-04
McKane, Joseph K. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C549S305000
Reexamination Certificate
active
06515147
ABSTRACT:
The present invention relates to 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one and to its ketonic tautomer form 3-(1-oxo-pentyl)-5-nitro-3H-benzofuran-2-one.
3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one is a new compound which may be used as a synthesis intermediate. In particular, it may be converted to 2-butyl-5-nitrobenzofuran by hydrolysis, decarboxylation and cyclisation, by simple heating in an acid medium.
2-butyl-5-nitrobenzofuran may act as an intermediate in the synthesis of an antiarrythmic, dronedarone.
The present invention provides, therefore, 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one corresponding to formula (I)
and its ketonic tautomer form, 3-(1-oxo-pentyl)-5-nitro-3H-benzofuran-2-one corresponding to formula (II)
SUMMARY OF THE INVENTION
The present invention also provides a process for the preparation of the compound corresponding to formula (I) and its ketonic tautomer form (II).
Finally, the present invention provides the use of the compound corresponding to formula (I) or its ketonic tautomer form (II) as a synthesis intermediate, particularly for the preparation of active pharmaceutical principles.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In particular, the present invention provides the compound corresponding to formula (I) and the preparation thereof.
This preparation is characterised in that 5-nitro-3H-benzofuran-2-one is reacted, at a temperature above 30° C., with pentanoic anhydride and a salt of pentanoic acid, optionally in the presence of pentanoic acid, then the resulting reaction mixture is acidified, and then the expected product is isolated.
This method of operating constitutes an improvement to the process described by J. N. Chatterjea, J. Indian Chem. Soc. Vol. 33 no. 3, 1956, p. 175-182 and J. Indian Chem. Soc. Vol. 34, no.4, 1957, p. 299-305.
This improvement to the process relates to the acidification of the reaction mixture at the end of the reaction which allows better isolation of the expected product. A second improvement relates to the reduction in the amount of acid anhydride required for the reaction.
Under preferential conditions for carrying out the process according to the invention, 1 mole of 5-nitro-3H-benzofuran-2-one is reacted with 1 to 5 moles of pentanoic anhydride, 0.1 to 2 moles of a salt of pentanoic acid, and 0 to 1.5 moles of pentanoic acid, then the resulting reaction mixture is acidified, and then the expected product is isolated, if desired.
Under other preferential conditions for carrying out the process according to the invention, one mole of 5-nitro-3H-benzofuran-2-one is reacted with two moles of pentanoic anhydride and one mole of a salt of pentanoic acid, then the resulting reaction mixture is acidified, then the expected product is isolated.
In the implementation of the process according to the invention, the salt of pentanoic acid may be a salt of sodium, potassium or of tertiary amine. This salt may be prepared extemporaneously, preferably in situ, from pentanoic acid and a base. The base may be sodium carbonate.
In the implementation of the process according to the invention, the resulting reaction mixture is brought into contact with an acid. This acid will be preferably dilute sulfuric acid; indeed, it permits better recovery of the expected final product.
Still under preferential conditions for carrying out the process, the crude product obtained may be recrystallised in an acid. This acid will be advantageously acetic acid.
The present invention also provides the use of the product corresponding to formula (I) or its tautomeric form (II) for the production of synthesis intermediates. In particular, it provides the production of 2-butyl-5-nitro-benzofuran-2-one which may act as an intermediate in the synthesis of an antiarrhythmic agent, dronedarone.
REFERENCES:
patent: 3248401 (1966-04-01), Tondeur et al.
patent: 4252817 (1981-02-01), Closse et al.
patent: 96/05190 (1996-02-01), None
EPO Search Report for EP Application No. 01810033, mail date Sep. 6, 2001.
J. N. Chatterjea: Journal of the Indian Chemical Society, vol. 33, No. 3, 1956, p. 175-182.
J. N. Chatterjea: Journal of the Indian Chemical Society, vol. 34 No. 4, 1957, p. 299-305.
Elix et al, Aust. J. Chem. (1973), 26 (5), 1079-91 CAS Abstract.
Mordacq Françoise
Schouteeten Alain
Clariant (France) S.A.
Hanf Scott E.
McKane Joseph K.
Saeed Kamal
LandOfFree
3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one a... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one a..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 3-(1-hydroxy-pentylidene)-5-nitro-3H-benzofuran-2-one a... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3171777