Claims
- 1. A process of synthesizing a carbapenem intermediate of the formula: ##STR25## comprising: treating a N-deprotected acetoxy compound of the formula: ##STR26## wherein R.sub.1 is H, trialkylsilyl, triarylsilyl, diarylalkylsilyl or aryldialkylsilyl, wherein the alkyl portions of said groups contain 1-4 carbon atoms, and the aryl portions of said groups are selected from the group consisting of phenyl, p-nitrobenzylcarbonate or phenyl substituted with one to three groups selected from C.sub.1 to C.sub.3 alkyl, halo, trifluoromethyl, amino, cyano and nitro;
- R.sub.4 represents C.sub.1-4 alkyl, C.sub.2-4 alkenyl, phenyl, phenyl substituted by one to three groups selected from C.sub.1 to C.sub.3 alkyl, halo, trifluoromethyl, amino, cyano and nitro,
- with a silyl enolether of the formula: ##STR27## wherein: R.sub.2 and R.sub.3 are independently H, C.sub.1 to C.sub.4 alkyl, C.sub.2 to C.sub.4 alkenyl, benzyl or phenethyl; and
- R.sub.5 represents benzyl, allyl, C.sub.1-4 alkyl, or p-nitrobenzyl,
- in the presence of a Lewis acid selected from the group consisting of zinc halide, boron trifluoride etherate, titanium tetrachloride, stannic chloride and aluminum chloride
- or a silylating agent having sufficient reactivity to yield said intermediate.
- 2. A process of synthesizing a carbapenem intermediate in accordance with claim 1, further comprising:
- cyclizing the intermediate: ##STR28## in the presence of rhodium (II) acetate to form a bicyclic ketoester of the formula: ##STR29##
- 3. A method of preparing intermediates for carbapenem antibiotics comprising the step of treating a N-deprotected acetoxy compound of the formula: wherein R.sub.1 is H, trialkylsilyl, triarylsilyl, diarylalkylsilyl or aryldialkylsilyl, with the alkyl groups having 1-4 carbon atoms and the aryl groups being phenyl or substituted phenyl or p-nitrobenzylcarbonate and R.sub.4 is alkyl of 1-4 carbon atoms alkenyl of 2-4 carbon atoms, phenyl, phenyl substituted by 1-3 alkyl groups of 1-3 carbon atoms, 1-3 halogen atoms, 1-3 trifluoromethyl groups, amino, cyano or nitro, with silyl enolether of the formula: ##STR30## wherein R.sub.2 and R.sub.3 are H or alkyl of 1-4 carbon atoms, alkenyl of 2-4 carbon atoms, benzyl or phenethyl and R.sub.5 is benzyl, allyl, alkyl of 1-4 carbons or p-nitrobenzyl, in the presence of a Lewis acid selected from the group consisting of zinc halide, boron trifluoride etherate, titanium tetrachloride, stannic chloride, and aluminum chloride or silylating agent having sufficient reactivity to yield said intermediate.
- 4. A method according to claim 3 wherein said step of treating is preceded by a step of deprotecting an acetoxy compound of the formula: ##STR31## wherein P is a readily removable nitrogen protecting group to produce a N-deprotected acetoxy compound.
RELATED APPLICATION
This is a continuation, of application Ser. No. 07/825,797, filed Jan. 21, 1992 abandoned, which is a continuation, of application Ser. No. 07/744,664, filed Aug. 9, 1991, abandoned, which is a continuation, of application Ser. No. 559,807, filed Jul. 30, 1990, now abandoned, which is a division of Ser. No. 463,020, filed Jan. 10, 1990, now abandoned, which is a continuation of Ser. No. 355,858, filed May 18, 1989, now abandoned, which is a continuation of Ser. No. 245,996, filed Sep. 14, 1988, now abandoned, which is a continuation of Ser. No. 212,107, filed Jun. 21, 1988, now abandoned, which is a division of Ser. No. 124,135, filed Nov. 23, 1987, now abandoned, which is a division of Ser. No. 065,189, filed Jun. 22, 1987, now abandoned, which is a continuation of Ser. No. 008,049, filed Jan. 15, 1987, now abandoned, which is a continuation of Ser. No. 872,715, filed Jun. 10, 1986, now abandoned, which is a continuation of Ser. No. 388,373. filed Jun. 14, 1982, now abandoned, which is a cont-in-part of Ser. No. 367,532 filed Apr. 12, 1982, now abandoned, which is a continuation-in-part of Ser. No. 314,152 filed Oct. 23, 1981, now abandoned.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
4287123 |
Liu |
Sep 1981 |
|
4290947 |
Christensen |
Sep 1981 |
|
Non-Patent Literature Citations (8)
Entry |
Karady, JACS 103, 6765(1981). |
Oida, "Recent Advance in the Chemistry of Beta Lactam Antibiotics", p.330-348. |
Reider, Tet. Letters 23, 379 (1982). |
Chen, Tet. Letters 1977, p4183. |
Paterson, Tet. Letters p 1519-1520 (1979). |
Neetz I Chem Abs 95, 424465s,(1981). |
Neetz II, Ang. Chem Int. Ed. 17, 48-9(1978). |
Rasmussen, Synthesis 1977, p. 91. |
Divisions (3)
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Number |
Date |
Country |
Parent |
463020 |
Jan 1990 |
|
Parent |
124135 |
Nov 1987 |
|
Parent |
065189 |
Jun 1987 |
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Continuations (10)
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Number |
Date |
Country |
Parent |
825797 |
Jan 1992 |
|
Parent |
744664 |
Aug 1991 |
|
Parent |
559807 |
Jul 1990 |
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Parent |
355858 |
May 1989 |
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Parent |
355858 |
May 1989 |
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Parent |
245996 |
Sep 1988 |
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Parent |
212107 |
Jun 1988 |
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Parent |
008049 |
Jan 1987 |
|
Parent |
872715 |
Jun 1986 |
|
Parent |
388373 |
Jun 1982 |
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Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
367532 |
Apr 1982 |
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Parent |
314152 |
Oct 1981 |
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