Claims
- 1. A process for preparing s-metoprolol having the formula: ##STR29## or a salt thereof with high enantiomeric purity, comprising the steps of: a) reacting (s)-3-isopropylamino-1,2-propanediol having the formula: ##STR30## with a chloroformic acid ester having the formula: ##STR31## wherein R' is an alkyl group having 1-3 carbon atoms or a phenyl group to form (s)-5-hydroxymethyl-3-isopropyloxazolidin-2-one having the formula: ##STR32## b) reacting the resulting compound from step a), having the formula VII with an activated sulfonic acid having the formula: ##STR33## wherein R' is tolyl and X is Cl, to form the sulfonic acid ester of the compound having formula II;
- c) enriching the amount of the compound having formula II from step b by crystallization of the ester;
- d) reacting the crystallized compound having formula II with 4-[2-methoxyethyl] phenol having the formula: ##STR34## (e) hydrolysing the resulting compound having the formula: ##STR35## to form s-metoprolol.
- 2. The process according to claim 1 wherein repeated recrystallization are carried out in step c).
- 3. The process according to claim 1 wherein the (s)-3-isopropylamino-1,2-propanediol has an S/R enantiomeric ratio of at least 98/2 and the (s)-metoprolol or salt formed has an S/R enantiomeric ratio greater than 99.0/1.0.
- 4. The process according to claim 2 wherein the s metoprolol or salt formed has an S/R enantiomeric ratio greater than 99.0/1.0.
- 5. The process according to claim 1 wherein the (s)-3-isopropylamino-1,2-propanediol has an S/R enantiomeric ratio of at least 95/5 and the (s)-metroprolol or salt formed has an S/R enantiomeric ratio greater than 99.0/1.0.
- 6. A process according to claims 1-5 wherein the compound having the formula V is isolated as the Sorbate.
- 7. A process for preparing a (S)-5-hydroxymethyl-3-isopropyloxazolidin-2-one sulfonic acid ester having the formula: ##STR36## or a salt thereof, with high enantiomeric purity, comprising a) reacting (S)-3-isopropylamino-1,2-propanediol having the formula: ##STR37## with a chloroformic acid ester having the formula: ##STR38## wherein R' is an alkyl group having 1-3 carbon atoms or a phenyl group, to the form of (S)-5-hydroxymethyl-3-isopropyloxazolidin-2-one having the formula: ##STR39## and b) reacted the compound having formula VII with an activated sulfonic acid having the formula: ##STR40## wherein R is tolyl and X is Cl, to form the ester of the compound having formula II and c) enriching the amount of the compound having formula II from step b) by crystallization of the ester.
- 8. The process according to claim 7 wherein repeated recrystallizations are carried out in step c).
Priority Claims (1)
Number |
Date |
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8801518 |
Apr 1988 |
SEX |
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Parent Case Info
This application is a continuation of application Ser. No. 341,787, filed on Apr. 21, 1989 now abandoned.
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Continuations (1)
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Number |
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Parent |
341787 |
Apr 1989 |
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