Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2002-03-07
2004-05-18
Morris, Patricia L. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06737529
ABSTRACT:
TITLE OF THE INVENTION
The present invention relates to an improved process for the preparation of 2-chloro-5-methylpyridine -3-carbaldehyde which is a useful intermediate for the preparation of a variety of pharmaceutical and pesticide products. In particular, the present invention pertains to the preparation of 2-chloro-5-methylpyridine -3-carbaldehyde having formula 1 as set forth below.
It pertains especially to the preparation of 2-chloro-5-methylpyridine-3-carbaldehyde with a high degree of selectivity.
BACKGROUND OF THE INVENTION
Several pyridine, quinoline, and isoquinoline compounds are important intermediates in that they have been reported as potential anti tumor agents (J.Med.Chem, 19,1209,1976; CA,85:116544q). Carbaldehyde derived products served as ulcer healing agents (Ger. offen DE 3324034,1984; CA,101:54936g), allergy inhibitors (EP 120483,1984; CA,102:95649e; EP120484,1984; CA,102:113500f), antiviral agents (CA,113:172015b), and useful as intermediates for pharmaceuticals (Ger.offen DE 4429465,1996,CA, 124:343116u).
There is only one method disclosed in the literature for the preparation of 2-chloro-5-methylpyridine-3-carbaldehyde in 12% yield. (J. C. S. Perkin. Trans 1,1173, 1984).
The present invention describes an improved process for the preparation of 2-chloro-5-methylpyridine-3-carbaldehyde from N-benzyl-N-(1-Propenyl) acetamide using Vilsemier reagent to achieve a 64% yield, compared to a reported 12% yield.
OBJECT OF THE INVENTION
The main object of the present invention is to provide an improved process for the preparation of 2-chloro-5-methylpyridine-3-carbaldehyde.
Another object of the present invention is to prepare 2-chloro-5-methylpyridine-3-carbaldehyde in higher yields.
SUMMARY OF THE INVENTION
Accordingly the present invention provides an improved process for the preparation of 2-chloro-5-methylpyridine-3-carbaldehyde which comprises reacting N-benzyl-N-(1-Propenyl) acetamide with dimethyl formamide mixed with diphosgene or triphosgene (Vilsmeier) reagent in a molar ratio of N-benzyl-N-(1-Propenyl) acetamide to Vilsmeier reagent in the range of about 0.02:0.35 to about 0.07:0.35, at a temperature in the range of about 0° C. to about 10° C. for about 1 to about 4 hrs, heating the above reaction mixture at a temperature ranging between about 70° C. to about 100° C. for about 4 to about 6 hrs followed by extraction with methylene chloride, and separating the organic layer followed by removal of solvent to obtain the desired product.
In an embodiment of the present invention the molar ratio of N-benzyl-N-(1-Propenyl) acetamide to Vilsemier reagent is preferably about 0.05: 0.35.
In another embodiment the reaction time is preferably 2 hrs.
In yet another embodiment the reaction temperature is preferably in the range of about 75° C. to about 90° C.
In still another embodiment the product yield is 64%.
DETAILED DESCRIPTION
In the improved process for the preparation of the 2-chloro-5-methylpyridine-3-carbaldehyde about 21.93 g (0.3 moles) of dimethylformamide is added to a well stirred and cooled 53.65 g (0.35 moles) of phosphorousoxytrichloride material at a temperature range of about 0° C. to about 20° C. for about 25 to about 35 minutes and then adding to it 9.45 g (0.05 moles) of N-benzyl-N-(1-Propenyl) acetamide at the temperature of about 0 to about 20° C. The above reaction mixture is further continued for 2 hours at a room temperature of about 25° C. The ice cold bath is removed and heated to about 75 to about 90° C. for about 4 to about 6 hours. A orange yellow organic mass is produced which is poured over 200 gms of ice cold water with constant stirring. The mass is then extracted with 2×200 ml of methylene chloride and the layers are separated and then dried over sodium sulfate and the solvent is removed under pressure.
The residue obtained is subjected to chromatographic purification over silicagel to give a 64% yield of 2-chloro-5-methylpyridine-3-carbaldehyde.
REFERENCES:
patent: 5708180 (1998-01-01), Beck et al.
patent: 6479664 (2002-11-01), Banda et al.
Chinaraju Bhimapaka
Raghavan Kondapuram Vijaya
Rao Vaidya Jayathirtha
Abelman ,Frayne & Schwab
Council of Scientific and Industrial Research
Morris Patricia L.
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