Copper-mediated oximation reaction

• US 4,675,398 A
• Filed: 08/16/1985
• Issued: 06/23/1987
• Est. Priority Date: 08/16/1985
• Status: Expired due to Term

• Current Assignee: ER Squibb & Sons LLC (Bristol-Myers Squibb Company)
• Original Assignee: E R Squibb & Sons Incorporated
• Inventors: Anderson, Carl F., Sedergran, Thomas C.
• Primary Examiner(s): Berch, Mark L.
• Application Number:
  US06/766,224
• Time in Patent Office: 676 Days
• Field of Search: 260/245.4, 260/245.2 R, 544/22, 544/25, 544/27, 544/28, 544/90, 540/355, 540/205, 540/222, 540/301, 540/225, 540/228, 540/227, 540/315
• US Class Current: 540/355
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The presence of a copper salt during the oximation of a β-lactam containing compound having glyoxylamino substituents of the formula ##STR1## by reaction with an aminooxy compound having the formula

H.sub.2 N--O--R.sub.a,

or a salt or ester thereof, results in a product wherein the ratio of syn isomer to anti isomer is increased.

Claims

1. In a process for the preparation of a β

-lactam containing antibiotic having an acylamino substituent of the formula ##STR13## said process comprising the oximation of a β

-lactam containing compound having a glyoxylamino substituent of the formula ##STR14## by reaction with an aminoxy compound having the formula

space="preserve" listing-type="equation">H.sub.2 N--O--R.sub.a,

or a salt or ester thereof, the improvement comprising the addition of a copper salt to the reaction mixture;

wherein R is an amino protecting group and R_a is carboxyalkyl.

2. A process in accordance with claim 1 wherein R_a is carboxymethyl.

3. A process in accordance with claim 1 wherein R_a is 1-carboxy-1-methylethyl.

4. A process in accordance with claim 1 wherein R is formyl, t-butyloxycarbonyl, benzyloxycarbonyl, chloroacetyl, or trichloroacetyl.

5. A process in accordance with claim 1 wherein R is formyl.

6. A process in accordance with claim 1 wherein the copper salt is a cupric halide, cupric sulfate, cupric acetate, cupric nitrate, cupric oxide, cupric carbonate, cupric perchlorate, cupric tetrafluoroborate, a cuprous halide, cuprous acetate or cuprous oxide.

7. In a process for the preparation of a compound having the formula ##STR15## said process comprising the oximation of a compound having the formula ##STR16## by reaction with an aminoxy compound having the formula

View Dependent Claims (8, 9, 10, 11, 12)

8. A process in accordance with claim 7 wherein R_a is carboxymethyl.

9. A process in accordance with claim 7 wherein R_a is 1-carboxy-1-methylethyl.

10. A process in accordance with claim 7 wherein R is formyl, t-butyloxycarbonyl, benzyloxycarbonyl, chloroacetyl, or trichloroacetyl.

11. A process in accordance with claim 7 wherein R is formyl.

12. A process in accordance with claim 7 wherein the copper salt is a cupric halide, cupric sulfate or cupric acetate.

13. In a process for the preparation of a compound having the formula ##STR17## said process comprising the oximation of a compound having the formula ##STR18## by reaction with an aminoxy compound having the formula ##STR19## or a salt or ester thereof, the improvement comprising the addition of a copper salt to the reaction mixture;

wherein R is an amino protecting group.

14. A process in accordance with claim 13 wherein R is formyl, t-butyloxycarbonyl, benzyloxycarbonyl, chloroacetyl, or trichloroacetyl.

15. A process in accordance with claim 13 wherein R is formyl.

16. A process in accordance with claim 13 wherein the copper salt is a cupric halide, cupric sulfate or cupric acetate, cupric nitrate, cupric oxide, cupric carbonate, cupric perchlorate, cupric tetrafluoroborate, a cuprous halide, cuprous acetate or cuprous oxide.