Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2001-08-24
2002-03-05
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
06353106
ABSTRACT:
The present invention concerns a process for preparing 3-cyano-8-substituted-8-azabicyclo[3.2.1]octanes. 3-Cyano-8-substituted-8-azabicyclo[3.2.1]octanes are useful as intermediates for certain insecticides (see, for example, WO 96/37494).
The present invention provides a process for the preparation of a compound of formula (I):
the process comprising the steps:
i. adding a solution of a compound of formula (II):
in aqueous hydrochloric acid to an aqueous solution of sodium cyanide at a temperature in the range −5 to 10° C.; and,
ii. mixing the resulting mixture at a pH in the range 8.5-9.5 and a temperature in the range −5 to 5° C. for 15-24 hours under efficient agitation conditions, the concentration of sodium cyanide in the resulting mixture being greater than 2.4 molar.
The solution of the compound of formula (II) in step (i) is preferably prepared by dissolving the compound of formula (II) in concentrated (about 36%w/w) hydrochloric acid and then adding an appropriate amount of cold water (preferably below 5° C.).
During Step (ii) the initial reaction mixture of a precipitate of compound (II) and compound (I) and the endo-cyano epimer of compound (I) is slowly converted to compound (I). In order to promote this two-phase reaction efficient agitation conditions sufficient to break the particles forming the solid phase (preferably high-shear conditions to enable a greater degree of particle breakage) are required. Such agitation conditions are fully described in Chapter 6 of “Mixing—principles and application” by S. Nagata, John Wiley 1975.
In one aspect the present invention provides a process as hereinbefore described wherein the pH range in step (ii) is 9.0-9.3.
In another aspect the present invention provides a process as hereinbefore described wherein, in step (ii), the concentration of sodium cyanide in the resulting mixture is greater than 3.5 molar.
In a further aspect the present invention provides a process as hereinbefore described wherein the agitation conditions of step (ii) are sufficient to break the particles of a precipitate forming a solid phase. In a still further aspect the present invention provides a process as hereinbefore describedwherein the agitation conditions are high-shear conditions.
In another aspect the present invention provides a process as hereinbefore described wherein step (ii) is conducted at a temperature in the range 0-2° C.
In a further aspect the present invention provides a process for the preparation of a compound of formula (I) comprising the steps:
i. adding a solution of a compound of formula (II) in aqueous hydrochloric acid to an aqueous solution of sodium cyanide at a temperature in the range −5 to 10° C. (preferably about 0° C.); and,
ii. mixing the resulting mixture at a pH in the range 8.5-9.5 (preferably 9.0-9.3) and a temperature in the range −5 to 5° C. (preferably about 0-2° C.) for 15-24 hours (preferably 17-20 hours) under efficient agitation conditions, the concentration of sodium cyanide in the resulting mixture being greater than 2.4 molar (preferably greater than 3.5 molar). In the following Examples, Examples 1 to 3 illustrate the invention.
REFERENCES:
patent: WO 96/37494 (1986-11-01), None
Nazarov, et al. (1956) “Heterocyclic Compounds. 45. Cyanhydrins of Gamma-Piperidones, Tetrahydro-Gamma-Pyrones and Tetrahydro-Gamma-Thiopyrones, Stereochemistry of the Cyanhydrin Synthesis” J. Gen Chem. 3545-3554.
Della, et al. (1990) “Rearrangement of Substituted Bicyclo ′2.2.1!hex-2-yl Mesylates Under Solvolytic Conditions” Aust. J. Chem. 43:1231-1244.
Iorio, et al. (1984) “Nitrogen analogues of phencyclidine: 1-alkyl-4-phenyl-4-(1-piperidinyl)piperidines” Farmaco Ed. Sci 39:599-611.
Sasaki, et al. (1978) “Synthesis of adamantane derivatives—38. Synthesis of 1,3-bishomoadamantane via ring-expansion of homoadamantan-2-one and homoadamant-4-en-2-one” Tetrahedron 34:67-71.
Binmore, et al. (1994) “Homolytic Reactions of Homocubane and Basketane: Rearrangement of the 9-Basketyl Radical by Multiple beta-Scissions” J. Am. Chem. Soc. 116:2759-2766.
Burgos, et al. (1992) “Synthesis, Structural Conformational and Biochemical Study of some 3beta-Acyloxytropan-3alpha-carboxylic Acid Hydrochlorides” 29:1821-1827.
Del Campo, et al. (1984) 145. Synthese facile de derives du diphenyl-2,4-aza-3-bicyclo ′3.3.1? nonane et du dipheny-7,9-aza-8-bicyclo ′4.3.1?decane Helv. Chim. Acta 67:1291-1297.
Matsuda, et al. (1992) “A Practical Synthesis of threo-3-Amino-2-hydroxycarboxylic Acids” Bull. Chem. Soc. Jpn 65:360-365.
Julia, et al. (1979) “Asymmetric Induction by Phase-Transfer Catalysis using Chiral Catalysts. Synthesis of 1,2-dichloroalkanes and acetylcyanohydrins” Tetrahedron Lett. 2171-2174.
Mcintosh, J.M. (1977) “Phase-Transfer Catalyzed Formation of Cyanohydrin Ethers and Acetates” Can. J. Chem. 55:4200-4205.
Hale and Dorr LLP
Morris Patricia L.
Syngenta Limited
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