Process for the preparaiton of alkyl fluorides

Details Process for the preparaiton of alkyl fluorides Process for the preparaiton of alkyl fluorides

1986-09-30

1989-11-07

Evans, J. E.

Chemistry of carbon compounds

Miscellaneous organic carbon compounds

C-metal

570142, C07C 1722, C07C 1902, C07C 7124, C17J 100

Patent

active

048790680

DESCRIPTION:

BRIEF SUMMARY
DESCRIPTION

This invention relates to a process for the preparation of alkyl fluorides by replacing an aliphatic hydroxy group with fluorine.
More particularly this invention relates to the reaction of a sulfonyl derivative of an aliphatic hydroxy group with an inorganic fluoride in a polyglycol.
The sulfonyl derivatives of this invention have the following general formula:
Although in formula I it is represented a single substituted hydroxy group the number of substituted aliphatic hydroxy groups on the R radical may be higher.
The aliphatic hydroxy group in formula I is primary or secondary in nature.
Typical examples of R' are those radicals known to form, together with --O--SO.sub.2 --, a leaving group.
Preferred examples of R' are methyl, phenyl, 4-methylphenyl, 2,4,6-trimethylphenyl, 2-naphthyl, and 2-pyridyl.
Typical examples of R are: straight and branched alkyl having from 1 to 22 C atoms, phenyl- and naphthyl-alkyl where the alkyl radical has 1-6 C atoms, cycloalkyl having 3-6 C atoms optionally comprised in a polycyclic system whose skeleton, hence substituents excluded, has up to 22 C atoms. In addition the alkyl, the aryl and the cycloalkyl moiety may in turn be substituted by other groups provided they are inert under the conditions of the process of this invention. Typical examples of such groups are the nitro, ether, thioether, hydroxy, ketone, aldehyde, ketal, thioketal, ester, acylamino and the heterocyclic group.
Examples of polycyclic systems are the compounds containing the following skeleton: ##STR1## such as cholestane, coprostane, androstane and variously functionalized and/or unsatured cholane.
Examples of alkyl fluorides which can be prepared according to this invention comprise 3-fluoro-D-alanine (J. Kollonitsch et al., J. Am. Chem. Soc. 98, 5591, 1976; Dolling et al., J.O.C. 43, 1634, 1978), alfa-fluoromethyl-Dopa (M. J. Jung et al., Life Sci. 24, 1037, 1979; A. L. Maycock et al., Biochemistry 19, 709, 1980), alfa-fluromethylglutamic acid (U.S. Pat. No. 4,004,996; D. Kno et al. Biochemistry 20, 506, 1981), 4-fluoromethyl-GABA (E.P. Appln. 0000036) alfa-fluoromethylamino acids (J. Kollonitsch et al., J.O.C. 40, 3808, 1975; J.O.C. 44, 771, 1979). The person skilled in the art will appreciate that when preparing these compounds the amino and the carboxylic groups must be properly protected according to usual techniques.
Other alkyl fluorides which can be prepared in accordance with this invention are some fluoro-derivatives of methaqualone (J. Tani et al., J. Med. Chem. 22, 95, 1979) and 4-fluoromethyl monobactam analogs (E.P. Appln 0114128; J. S. Skotnick et al. J. Antibiot. 36 (9) 1201, 1983).
Furthermore the process fo this invention allows to prepare some intermediate compounds such as 1-fluoro-2-bromo(or chloro)ethane, and 1-fluoro-2-amino-ethane hydrochloride which are useful in the preparation of 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-ox o-3-quinolinecarboxylic acid (Belgian Pat. No. 887,574) and N'-((1alfa, 2beta, 6alfa)-2,6-dihydroxycyclohexyl)-N-(2-fluoroethyl)-N-nitrosourea (T. P. Johnston et al., J. Med. Chem. 27(11), 1422, 1984), respectively.
Known fluorination agents show a number of drawbacks such as expensiveness, toxicity, explosiveness, perishability, and corrosiveness. Examples of such agents are sulfur tetrafluoride (Ang. Chem. Int. Ed. Engl. I, 467, 1962) which is expensive and toxic; diethylaminosulfotrifluoride or DAST (J.O.C. 40, 574, 1975) which is expensive and toxic and whose preparation is dangerous because explosions can occur; the fluoro(phenyl)phosphoranes (Th. Lett 4507, 1978) which are difficult to prepare, toxic, and usually promote the formation of various byproducts; 1-diethylamino-1,1-difluoro-2-chloro-2-fluoro-ethane or FAR (J.C.S. Perkin I 512, 1977; J.C. Res. (S) 46, 1980) which deteriorates easily, is expensive, requires anhydrous conditions, and can only be used with substrates which are fairly soluble in organic, aprotic and low polar solvents; and the hydrofluoric acid/pyridine system (Synthesis, 472, 19

REFERENCES:
patent: 3080431 (1963-03-01), Zappel et al.
patent: 3413321 (1968-11-01), Boswell
patent: 4263214 (1981-04-01), DeLuca et al.
patent: 4594467 (1986-06-01), Henneke et al.
patent: 4633026 (1986-12-01), Kolich

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