Claims
- 1. A process for the preparation of an antibacterially active .beta.-lactam compound of the formula (III): ##STR10## a salt thereof, or an ester thereof wherein R is alkyl of 1 to 6 carbon atoms, R.sup.1 is a hydrocarbon or heterocyclyl group; R.sup.2 is hydrogen or a pharmaceutically acceptable salt or ester, R.sup.3 is hydrogen or a pharmaceutically acceptable salt or in vivo hydrolysable ester, and Y is --S--C(CH.sub.3).sub.2 --, --S--CH.sub.2, or --Y.sup.1 --CH.sub.2 --C(Z).dbd., wherein Y.sup.1 is oxygen, sulphur or --CH.sub.2 -- and Z is hydrogen, halo, alkoxy of 1 to 6 carbon atoms, --CH.sub.2 Q or --CH.dbd.CH--Q wherein Q is hydrogen, halo, hydroxy, mercapto, cyano, pyridinium, carboxy or an ester thereof, alkoxy of 1 to 6 carbon atoms, acyloxy, aryl, heterocyclyl or heterocyclylthio which process comprises reacting a compound of formula (IV): ##STR11## where R.sup.1, and Y are as above defined and R.sup.x is hydrogen or a carboxyl blocking group, with a halogenating agent in the presence of an alkali metal alkoxide having an alkoxide group of formula --OR where R is alkyl of 1 to 6 carbon atoms whereby said alkali metal alkoxide acts both,
- (a) as a strong base to facilitate the action of said halogenating agent to produce an intermediate acylimine derivative of the compound of formula IV, and
- (b) as a source of the ion RO.sup.- where R is alkyl of 1 to 6 carbon atoms for in situ reaction with said intermediate, thereby to form said compound of formula III, and optionally thereafter converting the .beta.-lactam produced to a salt or ester thereof.
- 2. A process according to claim 1 wherein Y is --S--C(CH.sub.3).sub.2 --.
- 3. A process according to claim 1 wherein the alkali metal alkoxide is lithium alkoxide.
- 4. A process according to claim 1 wherein the alkali metal alkoxide is sodium alkoxide in admixure with lithium chloride.
- 5. A process for the preparation of an antibacterially active .beta.-lactam compound of the formula (III): ##STR12## a salt thereof, or an ester thereof wherein R is methyl; R.sup.1 is phenyl, p-hydroxyphenyl, 3,4-dihydroxyphenyl or 2- or 3- thienyl; R.sup.2 is hydrogen or a pharmaceutically acceptable salt or ester, R.sup.3 is hydrogen or a pharmaceutically acceptable salt or in vivo hydrolysable ester, and Y is --S--C(CH.sub.3).sub.2 --, which process comprises reacting a compound of formula (IV): ##STR13## where R.sup.1, and Y are as above defined and R.sup.x is hydrogen or a carboxyl blocking group, with a halogenating agent in the presence of an alkali metal methoxide whereby said alkali metal methoxide acts both,
- (a) as a strong base to facilitate the action of said halogenating agent to produce an intermediate acylimine derivative of the compound of formula IV, and
- (b) as a source of the methoxide ion for in situ reaction with said intermediate, thereby to form said compound of formula III, and optionally thereafter converting the .beta.-lactam produced to a salt or ester thereof.
- 6. A process for the preparation of an antibacterially active .beta.-lactam of the formula (V): ##STR14## or a pharmaceutically acceptable salt thereof wherein R.sup.4 is phenyl, p-hydroxyphenyl or 2- or 3-thienyl which process comprises reacting a salt of a compound of the formula (VI): ##STR15## wherein R.sup.4 is as above defined and R.sup.x is a carboxy-blocking group with a halogenating agent in the presence of an alkali metal methoxide which acts both,
- (a) as a strong base to facilitate the action of said halogenating agent to produce an intermediate acylimine derivative of the compound of formula (VI) and
- (b) as a source of the methoxide ion for in situ reaction with said intermediate, thereby to form said compound of formula (V), and if R.sup.x is other than a salt moiety, converting the group --CO.sub.2 R.sup.x to a free acid or salt.
- 7. A process according to claim 6 wherein the source of methoxide ions is lithium methoxide.
- 8. A process according to claim 6 wherein the compound of formula (VI) is in the form of a mono- or di-alkali metal salt.
- 9. A process according to claim 6, wherein the source of methoxide ions is sodium methoxide.
- 10. A process according to claim 6, wherein the source of methoxide ions is sodium methoxide in admixture with lithium chloride.
Priority Claims (1)
Number |
Date |
Country |
Kind |
8235568 |
Dec 1982 |
GBX |
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Parent Case Info
This is a continuation of application Ser. No. 07/622,329 filed Nov. 27, 1990, now abandoned; which is a continuation of application Ser. No. 07/422,121 filed Oct. 16, 1989, abandoned; which is a continuation of application Ser. No. 07/134,216 filed Dec. 17, 1987, abandoned; which is a continuation of application Ser. No. 06/560,444 filed Dec. 12, 1983, abandoned.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4447602 |
Firestone et al. |
May 1984 |
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Foreign Referenced Citations (5)
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Country |
1040620 |
Oct 1978 |
CAX |
1401059 |
Jul 1975 |
GBX |
1412886 |
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GBX |
1463468 |
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GBX |
1576796 |
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GBX |
Non-Patent Literature Citations (6)
Entry |
The Journal of Organic Chemistry, vol. 38, No. 7, pp. 1436-1437, Apr. 6, 1973. |
Journal of the American Chemical Society, vol. 95, No. 7, pp. 2403-2404, Apr. 4, 1973. |
Lann et al., Tetrahedron Letters, No. 14, pp. 1311-1313, (1974). |
The Journal of Organic Chemistry, vol. 38. No. 7, Apr. 6, 1973, pp. 1436-1437. |
Journal of the American Chemical Society, vol. 95, No.7, Apr. 4, 1973, pp. 2403-2404. |
W.H.W. Lunn et al.Tetrahedron Letters, No. 14, pp. 1311-1313, (1974). |
Continuations (4)
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Number |
Date |
Country |
Parent |
622329 |
Nov 1990 |
|
Parent |
422121 |
Oct 1989 |
|
Parent |
134216 |
Dec 1987 |
|
Parent |
560444 |
Dec 1983 |
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