US 2003/0199696 A1 · Preparation of quinoline-substituted carbonate and carbamate derivatives

Preparation of quinoline-substituted carbonate and carbamate derivatives

OwnerMichael S. Allen, Ramiya H. Premchandran +13inventors

InventorsMichael S. Allen, Ramiya H. Premchandran, Sou-Jen Chang, Stephen Condon, John A. DeMattei, Steven A. King, Lawrence Kolaczkowski, Sukumar Manna, Paul J. Nichols, Hemant H. Patel, Subhash R. Patel, Daniel J. Plata, Eric J. Stoner, Jien-Heh J. Tien, Steven J. Wittenberger

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Abstract

The invention relates to a process for preparing quinoline-substituted carbonate and carbamate compounds, which are important intermediates in the synthesis of 6-O-substituted macrolide antibiotics. The process employs metal-catalyzed coupling reactions to provide a carbonate or carbamate of formula (I) or (II) or a substrate that can be reduced to obtain the same.

Claims29

Dependent claims

A process of preparing a compound of the formula

R1—CH═CHCH2OC(O)—X—R2 (I),
wherein R1 is independently selected from hydrogen and quinolyl optionally substituted with one or more of:
(i) alkyl,
(ii) alkoxy,
(iii) aryl,
(iv) nitro, and
(v) halo;
R2 is C1-C10-alkyl;
X is —O— or —NR3;
R3 is hydrogen, C1-C6-alkyl or aryl;
or R2 and R3 taken together form an aromatic or non-aromatic ring,
comprising the steps of:
(a) preparing an intermediate selected from:
(i) R1—C≡CCH2OR4, wherein R4 is hydrogen or a hydroxy protecting group;
(ii) R1—CH═CHC(O)OR5, wherein R5 is C1 to C6 lower alkyl;
(iii) R1—CH═CHCH(OR6)(OR7), wherein R6 and R7 are independently C1 to C6 alkyl;
(iv) R1—CH═CHC(O)OH;
(v) R1—CH═CHCHO;
and
(vi) R1—C≡C—CH2—OC(O)—X—R2;
(b) reducing or deprotecting an intermediate obtained in step (a);
and
(c) optionally coupling the compound obtained from step (b) with an acylating reagent.

20 more elements

A process of preparing a compound of the formula:

13
X is —O— or —NR3—;
R1 is independently selected from hydrogen and quinolyl optionally substituted with one or more substituents selected from:
(i) alkyl,
(ii) alkoxy,
(iii) aryl,
(iv) nitro, and
(v) halo;
R2 is C1-C10-alkyl;
R3 is hydrogen or C1-C6-alkyl;
or R2 and R3 taken together form an aromatic or non-aromatic ring;
and
R8 is selected from the group consisting of:
(i) —CH═CH—R11, wherein R11 is hydrogen or alkyl;
and
(ii) —C≡CR11;
comprising the steps of:
(a) reacting a compound of the formula:
14
wherein X1 is a halide, with an organometallic compound of the formula R8—M or R8—M—X1, wherein R8 and X1 are as defined above and M is metal, and
(b) optionally hydrogenating the compound obtained in step (a), wherein R8 is alkynyl or substituted alkynyl, to afford the corresponding compound wherein R8 is alkenyl or substituted alkenyl.

18 more elements

Dependencies are inferred from the claim text.