Claims
- 1. A process for preparing a compound of formula III: ##STR15## wherein: R.sup.2 is NHCH(CO.sub.2 R.sup.3)CH.sub.2 CH.sub.2 CO.sub.2 R.sup.3 or OR.sup.3 ;
- R.sup.3 is independently at each occurrence a carboxy protecting group; and
- X is a bond or C.sub.1 -C.sub.4 alk-diyl;
- comprising:
- reacting a compound of formula IV: ##STR16## wherein: X and R.sup.2 are defined above for formula III;
- M is a metal cation; and
- n is 1 or 2;
- with a trialkylsilyl halide in a solvent.
- 2. The process according to claim 1 wherein the compound of formula IV is a compound wherein X is a bond, --CH.sub.2 --, or --CH.sub.2 CH.sub.2 -- and R.sup.2 is NHC*H(CO.sub.2 R.sup.3)CH.sub.2 CH.sub.2 CO.sub.2 R.sup.3 or OR.sup.3 where the configuration about the carbon atom designated * is L.
- 3. The process according to claim 2 wherein X is --CH.sub.2 --.
- 4. The process according to claim 1 wherein the compound of formula IV is a compound wherein M is an alkali metal cation, n is 1 and R.sup.2 is NHC*H(CO.sub.2 R.sup.3)CH.sub.2 CH.sub.2 CO.sub.2 R.sup.3 or OR.sup.3 where the configuration about the carbon atom designated * is L.
- 5. The process according to claim 4 wherein the alkali metal is sodium.
- 6. The process according to claim 1 wherein the solvent is acetonitrile, the trialkylsilyl halide is trimethylsilyl chloride, and the reaction is performed at a temperature between 50.degree. C. and 70.degree. C.
- 7. The process according to claim 6 wherein the compound of formula IV is a compound wherein M is sodium, n is 1, X is --CH.sub.2 --, and R.sup.2 is NHC*H(CO.sub.2 R.sup.3)CH.sub.2 CH.sub.2 CO.sub.2 R.sup.3 or OR.sup.3 where the configuration about the carbon atom designated * is L.
- 8. A process according to claim 1 further comprising:
- a) halogenating a compound of formula III to form a compound of formula V: ##STR17## wherein: R.sup.2 and X are as defined above for formula III; and
- halo is chloride, bromide, or iodide;
- in a solvent; and
- b) adding to the product of step a) a base and a compound of formula VI: and ##STR18## c) optionally removing carboxy protecting groups from the product of step b); and
- d) optionally salifying the product of step b) or step c) to afford a compound of formula VII: ##STR19## wherein: R is NHCH(CO.sub.2 R.sup.1)CH.sub.2 CH.sub.2 CO.sub.2 R.sup.1 or OR.sup.1 ; and
- R.sup.1 is independently at each occurrence hydrogen or a carboxy protecting group; or a pharmaceutical salt or solvate thereof.
- 9. A process according to claim 8 wherein the compound of formula V is a compound wherein X is a bond, --CH.sub.2 --, or --CH.sub.2 CH.sub.2 -- and R.sup.2 is NHC*H(CO.sub.2 R.sup.3)CH.sub.2 CH.sub.2 CO.sub.2 R.sup.3 or OR.sup.3 where the configuration about the carbon atom designated * is L.
- 10. A process according to claim 9 wherein step a) is performed at a temperature between 35.degree. C. and 45.degree. C.
- 11. A process according to claim 9 wherein the compound of formula VII is a compound wherein R is NHCH(CO.sub.2 R.sup.1)CH.sub.2 CH.sub.2 CO.sub.2 R.sup.1.
- 12. A process according to claim 11 wherein the compound of formula V is a compound wherein X is --CH.sub.2 --.
- 13. A process according to claim 12 wherein step c) is performed and the compound of formula VII is the sodium hydroxide base addition salt.
Parent Case Info
This application is a division of application Ser. No. 09/160,129, filed Sep. 24, 1998 now U.S. Pat. No. 6,013,828 published Jan. 11, 2000 which claims the benefit of U.S. Provisional Application No. 60/093,039 which, pursuant to 37 C.F.R. 1.53(c)(2), has a filing date of Sep. 26, 1997.
This application claims the benefit of U.S. application No. 60/093,039 with an accorded filing date of Sep. 26, 1997 which, pursuant to 37 C.F.R. 1.53 (b) (2) (ii), is a conversion of U.S. application No. 08/938,385, filed Sep. 26, 1997.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4260771 |
Cragoe, Jr. et al. |
Apr 1981 |
|
Non-Patent Literature Citations (1)
Entry |
Larock, R. C. et al. : Synthesis of aryl-substituted aldehydes and ketones via palladium-catalyzed coupling of aryl halides and non-allylic unsaturated alcohols. Tetrahed. Lett. vol. 30, pp. 6629-6632, 1989. |
Divisions (1)
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Number |
Date |
Country |
Parent |
160129 |
Sep 1998 |
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