Method for the preparation of hexahydro-furo-[2,3-b]furan-3-ol
AssigneeTibotec Pharmaceuticals Ltd.
InventorsBart Rudolf Romanie Kesteleyn, Dominique Louis Nestor Surleraux, Peter Jan Leonard Mario Quaedflieg
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Abstract
The present invention relates to a method for the preparation of hexahydro-furo[2,3-b]furan-3-ol as well as novel intermediates for use in said method. More in particular the invention relates to a stereoselective method for the preparation of hexahydro-furo[2,3-b]furan-3-ol, and to a method amenable to industrial scaling up.
Claims25
A method for the synthesis of hexahydro-furo[2,3-b]furan-3-ol of formula (7) starting from an intermediate of formula (1) wherein P1 and P2 represent each independently a hydrogen, a hydroxy-protecting group or may together form a vicinal-diol protecting group,
- transforming said intermediate of formula (1) into a nitromethane derivative of formula (3) wherein R1 represents alkyl, aryl or aralkyl, R2 represents hydrogen or C(═O)OR3, R3 represents alkyl, aryl or aralkyl, or R3, if present, and R1 taken together with the atoms to which they are attached may form a 6 to 8-membered cyclic group which may be optionally substituted with alkyl, aralkyl, or aryl,
- subsequently transforming said nitromethane derivative into a tetrahydrofuran derivative of formula (6) wherein OR4 represents an alcoholate,
- and then transforming the intermediate of formula (6) into hexahydro-furo[2,3-b]furan-3-ol of formula (7) by way of an intramolecular cyclisation reaction
An intermediate having the formula (3),
- wherein P1 and P2 represent each independently a hydrogen, a hydroxy-protecting group or may together form a vicinal-diol protecting group, R1 represents alkyl, aryl or aralkyl, R2 represents hydrogen or C(═O)OR3, R3 represents alkyl, aryl or aralkyl, or R3, if present, and R1 taken together with the atoms to which they are attached may form a 6 to 8-membered cyclic group which may be optionally substituted with alkyl, aralkyl, or aryl;
- provided that when R2 is hydrogen and P1 and P2 taken together form an isopropylidene, then R1 is other than methyl or ethyl.
An intermediate having the formula (4) or (4′),
- wherein R1 represents alkyl, aryl or aralkyl;
- R2 represents hydrogen or C(═O)OR3;
- R3 represents alkyl, aryl or aralkyl, or R3, if present, and R1 taken together with the atoms to which they are attached may form a 6 to 8-membered cyclic group which may be optionally substituted with alkyl, aralkyl, or aryl;
- OR4 represents an alcoholate.
An intermediate having the formula (5) or (5′),
- wherein OR4 represents an alcoholate.
Dependencies are inferred from the claim text.