Process for the enantioselective preparation of phenylisoserine derivatives

• US 5,292,921 A
• Filed: 11/13/1992
• Issued: 03/08/1994
• Est. Priority Date: 05/22/1990
• Status: Expired due to Fees

• Current Assignee: Rhone-Poulenc Rorer S.A.
• Original Assignee: Rhone-Poulenc Rorer S.A.
• Inventors: Grierson, David S., Denis, Jean-Noel, Greene, Andrew-Elliot, Correa, Arlene
• Primary Examiner(s): Dees, Jose G.
• Assistant Examiner(s): BARTS, SAMUEL A
• Application Number:
  US07/946,448
• Time in Patent Office: 480 Days
• Field of Search: 562/444, 562/450, 560/29, 560/27
• US Class Current: 560/29
• CPC Class Codes: C07C 231/18 by stereospecific synthesis
• CPC Class Codes: C07C 269/06 by reactions not involving the formation of carbamate groups
• CPC Class Codes: C07D 305/14 condensed with carbocyclic rings or ring systems
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

Process for the enantioselective preparation of phenylisoserine derivatives of general formula (I) ##STR1## from phenylglycine S(+) wherein R is a phenyl radical or a tert butoxy radical and R is an alcohol protective group.

Claims

1. Process for the enantioselective preparation of phenylisoserine derivatives of formula (I) ##STR9## in which R is a phenyl or tert-butoxy radical and R₁ is a protecting group for the alcohol group, comprising treating S(+)-phenylglycine with a reducing agent and an agent for introducing a benzoyl or t-butoxycarbonyl group to give an alcohol of formula V ##STR10## in which R is as defined above, which is oxidized and then reacted with a vinylmagnesium halide to give a product of the formula (VI) ##STR11## in which R is as defined above, the hydroxyl group of which is then protected by a group R₁ to give a product of formula (VII) ##STR12## in which R and R₁ are as defined above, which is oxidized to the product of formula (I).

2. Process according to claim 1 for the preparation of a product of formula (I) wherein R₁ is a protecting group for the alcohol group selected from methoxymethyl, 1-ethoxyethyl, benzyloxymethyl, (b-trimethylsilylethoxy)methyl, tetrahydropyranyl and 2,2,2-trichloroethoxycarbonyl radicals.

3. Process according to claim 1, wherein the S(+)-phenylglycine is reduced by means of a reducing agent selected from lithium aluminum halide and borane (BH₃), optionally in the form of a complex with dimethyl sulphide, and a reagent for introducing a benzoyl or t-butoxycarbonyl group is then reacted with the amino alcohol obtained.

4. Process according to claim 3, wherein the reagent for introducing a t-butoxycarbonyl group is di-t-butyl dicarbonate.

5. Process according to claim 3, wherein the reagent for introducing a benzoyl group is benzoyl chloride.

6. Process according to claim 1, wherein the S(+)-phenylglycine is treated with a reagent for introducing a benzoyl or t-butoxycarbonyl group, and the acid obtained is then reduced by means of a reducing agent selected from lithium aluminum hydride and borane (BH₃), optionally in the form of a complex with dimethyl sulphide.

7. Process according to claim 6, wherein the reagent for introducing a t-butoxycarbonyl group is di-t-butyl dicarbonate.

8. Process according to claim 6, wherein the reagent for introducing a benzoyl group is benzoyl chloride.

9. Process according to claim 1, wherein 2-phenyl-2-5-butoxycarbonylaminoethanol or 2-phenyl-2-benzoylaminoethanol is oxidized by means of an oxalyl chloride/dimethyl sulphoxide mixture, and the aldehyde obtained as an intermediate is then reacted with a vinylmagnesium halide to give 1-phenyl-1-t-butoxycarbonylamino-2- hydroxybut-3-ene or 1-phenyl-1-benzoylamino-2-hydroxybut-3-ene, the hydroxyl group of which is protected in accordance with known methods of preparing ethers and acetals.

10. Process according to claim 1, wherein 1-phenyl-1-t-butoxycarbonylamino-2-hydroxybut-3-ene or 1-phenyl-1-benzoylamino-2-hydroxybut-3-ene, the hydroxyl group of which is protected, is oxidized by means of an alkali metal periodate in the presence of a catalytic amount of a ruthenium salt, or by means of potassium permanganate, and the phenylisoserine derivative of formula (I is then isolated.