Process for making spirolactone compounds

1. A process for preparing a compound of the formula IC, or a salt thereof,

T, U, V and W are each independently selected from the group consisting of

(1) nitrogen, and

(2) methine,

wherein the methine group is unsubstituted or optionally substituted with a substituent selected from the group consisting of

(a) halogen,

(b) lower alkyl,

(c) hydroxy, and

(d) lower alkoxy, and

wherein at least two of T, U, V, and W are methine;

comprising the steps of

(a) combining a strong base with a compound of formula A

in an aprotic solvent to form a solution;

(b) reacting a compound of formula B

R 2 is selected from the group consisting of:

(a) lower alkyl, and

(b) —CH 2 -phenyl, wherein the phenyl group is unsubstituted or substituted with a substituent selected from the group consisting of

(1) lower alkyl,

(2) lower alkoxy, and

(3) —NO 2 ,

with the solution of step (a) to form a solution;

(c) reacting the solution of step (b) with water to form a solution; and

(d) adjusting the pH of the solution of step (c) to between about 0 and 4 with an acid to afford the compound IC, or a salt thereof.

2. The process of claim 1 further comprising the step (e) of isolating the compound of formula IC, or a salt thereof.

3. The process of claim 1 wherein the aprotic solvent of step (a) is selected from the group consisting of tetrahydrofuran, toluene, heptane, dimethoxyethane, benzene, and hexane, diethyl ether, xylene, or a mixture thereof.

4. The process of claim 1 wherein the strong base of step (a) is selected from the group consisting of n-BuLi, sec-BuLi, t-BuLi, LiHMDS, NaHMDS, KHMDS and LiTMP.

5. The process of claim 1 wherein step (a) further comprises adding a salt selected from the group consisting of LiBr, LiCl, LiI, LiBF 4 , LiClO 4 , and CeCl 3 .

6. The process of claim 1 wherein R 2 is selected from the group consisting of —CH 3 , —CH 2 CH 3 , —(CH 2 ) 2 CH 3 , —CH(CH 3 ) 2 , —(CH 2 ) 3 CH 3 , and —CH(CH 3 ) 3 .

7. The process of claim 1 wherein the acid of step (d) is selected from the group consisting of hydrochloric acid, sulfuric acid, methane sulfonic acid, trifluoromethane sulfonic acid, and or a mixture thereof.

8. The process of claim 1 wherein T, V and W are methine, wherein the methine group is unsubstituted or optionally substituted with a substituent selected from the group consisting of

(a) halogen,

(b) lower alkyl,

(c) hydroxy, and

(d) lower alkoxy; and

U is nitrogen.

9. The process of claim 1 wherein T, V and W are unsubstituted methine; and U is nitrogen.

10. The process of claim 1 wherein T, U, V and W are methine, wherein the methine group is unsubstituted or optionally substituted with a substituent selected from the group consisting of

(a) halogen,

(b) lower alkyl,

(c) hydroxy, and

(d) lower alkoxy.