Claims
- 1. A process for the preparation of a compound having the formula IV: ##STR11## or an alkali salt thereof; wherein:
- R.sup.1, R.sup.2, R.sup.4, and R.sup.5 are independently selected from:
- (a) hydrogen,
- (b) C.sub.1 -C.sub.6 -alkyl,
- (c) C.sub.1 -C.sub.6 -alkoxy,
- (d) --OH,
- (e) --CO.sub.2 H,
- (f) --CO.sub.2 (C.sub.1 -C.sub.6 -alkyl),
- (g) --N(C.sub.1 -C.sub.6 -alkyl).sub.2,
- or R.sup.1, R.sup.2, R.sup.3, R.sup.4, or R.sup.5 on adjacent ring carbons may be combined to form a --O--(CH.sub.2).sub.n --O-- residue;
- provided that at least one of R.sup.1, R.sup.2, R.sup.4, or R.sup.5 is --CO.sub.2 H;
- R.sup.3 is C.sub.1 -C.sub.6 -alkoxy or --N(C.sub.1 -C.sub.6 -alkyl).sub.2, or R.sup.2 and R.sup.3 or R.sup.3 and R.sup.4 are combined to form a --O--(CH.sub.2).sub.n --O-- residue; and
- n is 1 to 3;
- which comprises:
- treating an aromatic compound of the formula V: ##STR12## in an aqueous alkali solution with a brominating agent selected from:
- (a) N-bromosuccinimide, and
- (b) 1,3-dibromo-5,5-dimethylhydantoin;
- at a temperature and for a length of time sufficient to optimally convert the compound of formula V to the compound of formula IV or a salt thereof; and
- then optionally treating the reaction mixture with an acid to afford the compound of formula IV.
- 2. The process of claim 1 wherein the amount of the brominating agent employed is selected from a value in the range between 0.505 to 1.5 molar equivalents with respect to the compound of the formula V.
- 3. The process of claim 1 wherein the brominating agent is N-bromosuccinimide.
- 4. The process of claim 3 wherein the aqueous alkali solution is a solution of sodium hydroxide in water.
- 5. The process of claim 3 wherein the aqueous alkali solution is a solution of potassium hydroxide in water.
- 6. The process of claim 1 wherein the acid is an aqueous acidic solution.
- 7. The process of claim 6 wherein the aqueous acidic solution is aqueous hydrobromic acid.
- 8. The process of claim 6 wherein the aqueous acidic solution is aqueous hydrochloric acid.
- 9. The process of claim 1 wherein the brominating agent is 1,3-dibromo-5,5-dimethylhydantoin.
- 10. The process of claim 9 wherein the amount of the 1,3-dibromo-5,5-dimethylhydantoin utilized in the process relative to the amount of compound V is selected from 0.505 to 0.55 molar equivalents amd the amount of alkali base in the aqueous alkali solution relative to the amount of compound V is selected from 1.01 to 1.1 molar equivalents.
- 11. The process of claim 9 wherein the aqueous alkali solution is a solution of sodium hydroxide in water.
- 12. A process for the preparation of a compound, having the formula IVa: ##STR13## which comprises: treating a benzoic acid of the formula Va: ##STR14## in an aqueous alkali solution with a brominating agent selected from:
- (a) N-bromosuccinimide, and
- (b) 1,3-dibromo-5,5-dimethylhydantoin;
- at a temperature and for a length of time sufficient to optimally convert the compound of formula Va to the compound of formula IVa or a salt of the compound of formula IVa; and
- then optionally treating the reaction mixture with an acid.
- 13. The process of claim 12 wherein the amount of the brominating agent employed is selected from a value in the range between 0.505 to 1.5 molar equivalents with respect to the compound of the formula Va.
- 14. The process of claim 12 wherein the brominating agent is N-bromosuccinimide.
- 15. The process of claim 14 wherein the aqueous alkali solution is selected from: a solution of sodium hydroxide in water or a solution of potassium hydroxide in water.
- 16. The process of claim 12 wherein the temperature is selected from a temperature between 23.degree. and 29.degree. C.
- 17. The process of claim 12 wherein the acid is an aqueous acidic solution.
- 18. The process of claim 17 wherein the aqueous acidic solution is aqueous hydrobromic acid.
- 19. The process of claim 17 wherein the aqueous acidic solution is aqueous hydrochloric acid.
- 20. The process of claim 12 wherein the compound having the formula IVa is subsequently employed in the preparation of remoxipride.
- 21. The process of claim 12 wherein the brominating agent is 1,3-dibromo-5,5-dimethylhydantoin.
- 22. The process of claim 21 wherein the amount of the 1,3-dibromo-5,5-dimethylhydantoin utilized in the process relative to the amount of compound Va is selected from 0.505 to 0.55 molar equivalents amd the amount of alkali base in the aqueous alkali solution relative to the amount of compound Va is selected from 1.01 to 1.1 molar equivalents.
- 23. The process of claim 21 wherein the aqueous alkali solution is a solution of sodium hydroxide in water.
RELATED APPLICATION
The present patent application is a continuation-in-part of copending application Ser. No. 730,364, filed Jul. 15, 1991, abandoned.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
4232037 |
Florvall |
Nov 1980 |
|
4789683 |
Florvall et al. |
Dec 1988 |
|
Non-Patent Literature Citations (6)
Entry |
CA 77(5):34088g 1972. |
CA 100 (17):138334b 1984. |
CA 114 (1):6013a 1989. |
J. S. Pizey, N-Bromosuccinimide, Synthetic Reagents, 2, 1 (John Wiley New York, 1974). |
L. Florvall and Sven-Ove Ogren, J. Med. Chem., 25, 1280 (1982). |
V. Oakes et al., J. Chem. Soc., 4678 (1962). |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
730364 |
Jul 1991 |
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