Production of oxetanones
AssigneeHoffmann-La Roche Inc.
InventorsMartin Karpf, Ulrich Zutter
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Abstract
The invention relates to a novel process for producing a compound having the formula ##STR1## wherein R.sup.1, R.sup.2 and X are described herein, via corresponding .beta.-keto- and .beta.-hydroxy-.delta.-lactones, as well as novel intermediates which occur in the process.
Drawings
Claims13
A process for the preparation of a compound having the formula ##STR15## where R.sup.1 and R.sup.2 each are independently (i) alkyl having from 1 to 17 carbon atoms, alkyl-O-alkyl having up to 17 total carbon atoms in which the oxygen atom is in a position other than the .alpha. or .beta.-position or (iii) benzyl optionally ring-substituted by 1 to 3 C.sub.1-6 -alkyl or C.sub.1-6 -alkoxy groups,
- which process comprises the steps of:
- a) saponifying a .beta.-hydroxyester of the formula
- R.sup.2 --CHOHCH.sub.2 COO--R VIII
- wherein R is C.sub.1-4 -alkyl;
- b) reacting the imidazolide of the resulting .beta.-hydroxyacid of the formula
- R.sup.2 --CHOHCH.sub.2 COOH IX
- with the Mg salt of the malonic acid ester derivative of the formula
- HOCOCH(R.sup.1)CO0--R X
- c) cyclizing the resulting .delta.-hydroxy-.beta.-ketoester of the formula
- R.sup.2 --CHOHCH.sub.2 COCH(R.sup.1)COO--R XI
- and
- d) catalytically hydrogenating the resulting .beta.-keto-.delta.-lactone of the formula ##STR16## to form a compound of formula II.
A process for the preparation of a compound having the formula ##STR17## where R.sup.1 and R.sup.2 each are independently (i) alkyl having from 1 to 17 carbon atoms, (ii) alkyl-O-alkyl having up to 17 total carbon atoms in which the oxygen atom is in a position other than the .alpha. and .beta.-position, or (iii) benzyl optionally ring-substituted by 1 to 3 C.sub.1-6 -alkyl or C.sub.1-6 -alkoxy groups, which process comprises the steps of:
- a) reacting a .beta.-ketoester of the formula
- CH.sub.3 COCH(R.sup.1)COO--R XIII
- wherein R is C.sub.1-4 -alkyl with an ester of the formula
- R.sup.2 --COO--R XIV
- b) cyclizing the resulting diketoester of the formula
- R.sup.2 --COCH.sub.2 COCH(R.sup.1)COO--R XV
- and
- c) catalytically hydrogenating the resulting pyrone of the formula ##STR18## to form a compound of formula II.
A process for the preparation of a compound having the formula ##STR19## wherein R.sup.1 and R.sup.2 each are independently (i) alkyl having from 1 to 17 carbon atoms, (ii) alkyl-O-alkyl having up to 17 total carbon atoms in which the oxygen atom is in a position other than the .alpha. and .beta.-position, or (iii) benzyl optionally ring-substituted by 1 to 3 C.sub.1-6 -alkyl or C.sub.1-6 -alkoxy groups;
- which process comprises the steps of:
- a) reacting a .beta.-ketoester of the formula
- CH.sub.3 COCH(R.sup.1)COO--R XIII
- where R is C.sub.1-4 alkyl, with an aldehyde of the formula
- R.sup.2 --CHO XVII
- and
- b) cyclizing the resulting .delta.-hydroxy-.beta.-ketoester of the formula XI
- R.sup.2 --CHOHCH.sub.2 COCH(R.sup.1)COO--R XI
- to form a compound of formula XII.
A process for the preparation of a compound having the formula ##STR20## where R.sup.1 and R.sup.2 each are independently (i) alkyl having from 1 to 17 carbon atoms, (ii) alkyl-O-alkyl having up to 17 total carbon atoms in which the oxygen atom is in a position other than the .alpha. or .beta.-position, or (iii) benzyl optionally ring-substituted by 1 to 3 C.sub.1-6 -alkyl or C.sub.1-6 -alkoxy groups,
- which process comprises the steps of:
- a) etherifying a .beta.-hydroxyester having the above formula
- R.sup.2 --CHOHCH.sub.2 COO--R VIII
- wherein R is C.sub.1-4 -alkyl
- b) saponifying the resulting ether of the formula
- R.sup.2 --CH(OCH.sub.2 --AR)CH.sub.2 COO--R XVIII
- wherein Ar is phenyl substituted by 1 to 3 groups R.sup.9 or OR.sup.9, where R.sup.9 is hydrogen or C.sub.1-3 -alkyl,
- c) halogenating the resulting ether acid of the formula
- R.sup.2 --CH(OCH.sub.2 --AR)CH.sub.2 COOH XIX
- d) reacting the resulting acid halide with Meldrum's acid;
- e) hydrogenolyzing the resulting compound of the formula ##STR21## cyclizing to a .beta.-keto-.delta.-lactone of the formula ##STR22## and f) reacting the .beta.-keto-.delta.-lactone of formula XXI with an aldehyde which introduces the group R.sup.1 or --CH.sub.2 --R.sup.11 and which has the formula
- R.sup.11 --CHO XXII
- and
- wherein R.sup.11 together with the methylene group to which it is attached represents the group R.sup.1,
- to give the compound of formula XII above.
A process for the preparation of a compound having the formula ##STR23## where R.sup.2 is (i) alkyl having from 1 to 17 carbon atoms, ii) alkyl-O-alkyl having from 4 to 17 total carbon atoms in which the oxygen atom is in a position other than the .alpha. or .beta.-position, or (iii) benzyl optionally ring-substituted by 1 to 3 C.sub.1-6 -alkyl or C.sub.1-6 -alkoxy groups,
- which process comprises the steps of:
- a) reacting the imidazolide of the .beta.-hydroxyacid of the formula
- R.sup.2 --CHOHCH.sub.2 COOH IX
- with the Mg salt of a mono-lower alkyl malonate and
- b) cyclizing the resulting .delta.-hydroxy-.beta.-ketoester of the formula
- R.sup.2 --CHOHCH.sub.2 COCH.sub.2 COO--R XXIII
- to give the compound of formula XXI above.
A compound having the formula:
- ##STR24## wherein R.sup.1 and R.sup.2 each are independently (i) alkyl having from 1 to 17 carbon atoms, (ii) alkyl-O-alkyl having up to 17 total carbon atoms in which the oxygen atom is in a position other than the .alpha.- or .beta.-position, or (iii) benzyl optionally ring-substituted by 1 to 3 C.sub.1-6 -alkyl or C.sub.1-6 -alkoxy groups.
A compound having the formula:
- ##STR25## wherein R.sup.1 and R.sup.2 each are independently (i) alkyl having from 1 to 17 carbon atoms, (ii) alkyl-O-alkyl having up to 17 total carbon atoms in which the oxygen atom is in a position other than the .alpha.- or .beta.-position, or (iii) benzyl optionally ring-substituted by 1 to 3 C.sub.1-6 -alkyl or C.sub.1-6 -alkoxy groups.
A compound having the formula:
- ##STR26## wherein R.sup.1 and R.sup.2 each are independently (i) alkyl having from 1 to 17 carbon atoms, (ii) alkyl-O-alkyl having up to 17 total carbon atoms in which the oxygen atom is in a position other than the .alpha.- or .beta.-position, or (iii) benzyl optionally ring-substituted by 1 to 3 C.sub.1-6 -alkyl or C.sub.1-6 -alkoxy groups.
A compound having the formula ##STR27## wherein R.sup.21 is alkyl with from 9 to 17 C atoms optionally interrupted by an O atom in a position other than the .alpha. or .beta.position.
Dependencies are inferred from the claim text.