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US 5,594,153 AGranted
Process for the preparation of 1,3-dioxane derivatives useful in the preparation of HMG-COA reductase inhibitors
AssigneeE. R. Squibb & Sons, Inc.
InventorsJohn K. Thottathil, Yadagiri Pendri, Wen-Sen Li, David R. Kronenthal
Life of this patent
Estimating the term…
Abstract
A novel, overall process for the preparation of a compound of the formula I: ##STR1## where R.sup.1 and R.sup.2 are each independently hydrogen, an alkyl group, a cycloalkyl group, an aryl group or, taken together with the carbon atom to which they are attached, form a cycloalkyl group; and R.sup.3 is hydrogen, an alkyl group, or an aryl group, or salts thereof, useful as intermediates in the preparation of HMG-CoA reductase inhibitors; novel methods within the overall process; and novel intermediates produced by those methods.
Claims11
A method for the preparation of a compound of the formula VII:
- ##STR40## where X is a halogen atom;
- R.sup.1 and R.sup.2 are each independently hydrogen, an alkyl group, a cycloalkyl group, an aryl group or, taken together with the carbon atom to which they are attached, form a cycloalkyl group;
- and
- R.sup.3 is hydrogen, an alkyl group or an aryl group,
- or a pharmaceutically acceptable salt thereof,
- comprising the step of reacting a compound of the formula V:
- ##STR41## where X and R.sup.3 are as defined in the formula VII, or a pharmaceutically acceptable salt thereof, with a compound of the formula VIa, VIb or VIc:
- ##STR42## where R.sup.1 and R.sup.2 are as defined in the formula VII;
- R.sup.1b and R.sup.2b are each independently hydrogen, an alkyl group, a cycloalkyl group, an aryl group or, taken together with the carbon atoms to which they are attached, form a 1,2-cycloalkenyl group;
- and
- R.sup.5 and R.sup.6 are each independently an alkyl group, in the presence of an acidic condensation agent,
- wherein alkyl employed herein alone or as part of another group has from 1 to 21 carbons;
- cycloalkyl employed herein alone or as part of another group has from 3 to 21 carbons;
- aryl employed herein alone or as part of another group has from 6 to 12 carbons;
- cycloalkenyl employed herein alone or as part of another group has from 3 to 21 carbons.
12 more elements
A compound of the formula VII:
- ##STR45## where X is a halogen atom;
- R.sup.1 and R.sup.2 are each independently hydrogen, an alkyl group, a cycloalkyl group, an aryl group or, taken together with the carbon atom to which they are attached, form a cycloalkyl group;
- and
- R.sup.3 is hydrogen, an alkyl group, or an aryl group,
- or a pharmaceutically acceptable salt thereof,
- wherein alkyl employed herein alone or as part of another group has from 1 to 21 carbons;
- cycloalkyl employed herein alone or as part of another group has from 3 to 21 carbons;
- aryl employed herein alone or as part of another group has from 6 to 12 carbons.
5 more elements
A method for the preparation of a compound of the formula VIII:
- ##STR47## where R.sup.1 and R.sup.2 are each independently hydrogen, an alkyl group, a cycloalkyl group, an aryl group or, taken together with the carbon atom to which they are attached, form a cycloalkyl group;
- R.sup.3 is hydrogen, an alkyl group or an aryl group;
- and
- R.sup.7 is an alkyl group or an aryl group;
- or a pharmaceutically acceptable salt thereof, comprising the step of displacing the group X of a compound of the formula VII:
- ##STR48## where x is a halogen atom;
- and
- R.sup.1, R.sup.2 and R.sup.3 are as defined in the formula VIII,
- or a pharmaceutically acceptable salt thereof, with an acyloxy group of the formula --O--C(O)--R.sup.7, by use of a displacement agent,
- wherein alkyl employed herein alone or as part of another group has from 1 to 21 carbons;
- cycloalkyl employed herein alone or as part of another group has from 3 to 21 carbons;
- aryl employed herein alone or as part of another group has from 6 to 12 carbons.
9 more elements
A compound of the formula VIII:
- ##STR52## where R.sup.1 and R.sup.2 are each independently hydrogen, an alkyl group, a cycloalkyl group, an aryl group or, taken together with the carbon atom to which they are attached, form a cycloalkyl group;
- R.sup.3 is hydrogen, an alkyl group or an aryl group;
- and
- R.sup.7 is an alkyl group,
- of a pharmaceutically acceptable salt thereof,
- wherein alkyl employed herein alone or as part of another group has from 1 to 21 carbons;
- cycloalkyl employed herein alone or as part of another group has from 3 to 21 carbons;
- aryl employed herein alone or as part of another group has from 6 to 12 carbons.
5 more elements
A method for the preparation of a compound of the formula I:
- ##STR54## where R.sup.1 and R.sup.2 are each independently hydrogen, an alkyl group, a cycloalkyl group, an aryl group or, taken together with the carbon atom to which they are attached, form a cycloalkyl group;
- and
- R.sup.3 is hydrogen, an alkyl group, or an aryl group;
- or a pharmaceutically acceptable salt thereof:
- ##STR55## where R.sup.1, R.sup.2 and R.sup.3 are as defined in the formula I, and
- (i) R.sup.7 is an alkyl group;
- or
- (ii) said hydrolysis is conducted employing a mild base and/or a mildly basic medium and R.sup.7 is an alkyl group or an aryl group,
- wherein alkyl employed herein alone or as part of another group has from 1 to 21 carbons;
- cycloalkyl employed herein alone or as part of another group has from 3 to 21 carbons;
- aryl employed herein alone or as part of another group has from 6 to 12 carbons.
8 more elements
Dependencies are inferred from the claim text.