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US 2004/0073049 A1Published application
Process for preparing intermediates for the manufacture of discodermolide and discodermolide analogues
AssigneeNovartis AG
InventorsGuido Koch, Olivier Loiseleur, Gottfried Sedelmeier
Life of this patent
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Abstract
The invention relates to a process for the preparation of a substituted alkene of formula (I) wherein R1, R2 and R3 are independently of each other a protecting group for a hydroxy group or hydrogen and R4 is phenyl which is unsubstituted or mono- or disubstituted by alkoxy, which alkene constitutes an intermediate for the preparation of discodermolide and discodermolide analogues.
Claims17
A process for preparing a substituted alkene of formula I
- 38
- wherein
- R1, R2 and R3 are independently of each other a protecting group for a hydroxy group or hydrogen and
- R4 is phenyl which is unsubstituted or mono- or disubstituted by alkoxy,
- in which process a sulfonate of formula (II),
- 39
- wherein R1, R2 and R3 are all protecting groups for a hydroxy group which protecting groups can be identical or different, R4 has the meaning as defined for the compound of formula I and R5 is alkyl or aryl which is unsubstituted or substituted by alkyl,
- is reduced and afterwards, If desired, one, two or all protecting groups R1, R2 and R3 are split off.
5 more elements
A process for preparing a substituted alkene of formula I
- 40
- wherein
- R1, R2 and R3 are independently of each other a protecting group for a hydroxy group or hydrogen and
- R4 is phenyl which is urisubstituted or mono- or disubstituted by alkoxy,
- in which process a carboxylic ester of the formula III
- 41
- wherein R1, R2 and R3 are all protecting groups for a hydroxy group which protecting groups can be identical or different, R6 is alkyl or arylalkyl, and R4 has the meaning as defined for the compound of formula I,
- is first reduced, the obtained alcohol of the formula IV
- 42
- wherein R1, R2, R3 and R4 have the meanings as defined for the compound of formula III, is further reacted with a compound of formula V
- R5SO2Hal (V)
- wherein R5 is alkyl or aryl which is unsubstituted or substituted by alkyl, and Hal represent halogen, and the obtained sulfonate of formula II
- 43
- wherein
- R1, R2, R3 and R4 have the meanings as defined for the carboxylic ester of formula III and R5 is alkyl or aryl which is unsubstituted or substituted by alkyl, is further reduced,
- and, if desired, one, two or all protecting groups R1, R2 and R3 are detached by methods known in the art.
13 more elements
A process for preparing a carboxylic ester of formula III
- 44
- wherein
- R1 and R2 are protecting groups for a hydroxy group which protecting groups can be identical or different or hydrogen, R3 is hydrogen, R4 is phenyl which is unsubstituted or mono- or disubstituted by alkoxy, and R6 is alkyl or arylalkyl,
- in which process an allyl halide of the formula VI
- 45
- wherein R1 and R2 have the meanings as defined for a carboxylic ester of formula III and X is halogen,
- is reacted with a carboxylic ester of formula VII
- 46
- wherein R3, R4 and R6 have the meanings as defined for a carboxylic ester of formula III in the presence of a base,
- and afterwards, if desired, one or all protecting groups R1 and R2 are split off.
7 more elements
A sulfonate of formula II
- 47
- wherein R1, R2 and R3 are all protecting groups for a hydroxy group which protecting groups can be identical or different, R4 is phenyl which is unsubstituted or mono- or disubstituted by alkoxy, and R5 is alkyl or aryl which is unsubstituted or substituted by alkyl.
A carboxylic ester of formula III
- 48
- wherein R1 and R2 are protecting groups for a hydroxy group which protecting groups can be identical or different, R3 is a protecting group for a hydroxy group or hydrogen, R4 is phenyl which is unsubstituted or mono- or disubstituted by alkoxy, and R6 is alkyl or arylalkyl.
An alcohol of formula IV
- 49
- wherein R1, R2 and R3 are all protecting groups for a hydroxy group which protecting groups can be identical or different and R4 is phenyl which is unsubstituted or mono- or disubstituted by alkoxy.
A carboxylic ester of formula VII
- 50
- wherein R3 is hydrogen, R4 is phenyl which is unsubstituted or mono- or disubstituted by alkoxy, and R6 is alkyl or arylalkyl.
An oxazolidinone of formula VIII
- 51
- wherein
- Ph denotes phenyl, and
- R1 and R2 are independently of each other a silyl protecting group, hydrogen or benzyl which is unsubstituted or mono- or disubstituted by lower alkoxy, or
- R1 and R2 together represent methyliden substituted by phenyl which phenyl group is monoor disubstituted by lower alkoxy.
2 more elements
An oxazolidinone of formula IX
- 52
- wherein Ph denotes phenyl, and R′ and R2 are independently of each other a silyl protecting group, hydrogen or benzyl which is unsubstituted or mono- or disubstituted by lower alkoxy under the proviso that one of both radicals R′ and R2 is a silyl protecting group.
A δ-valerolactol of the formula X
- 53
- wherein R2 is a protecting group for a hydroxy group.
An alcohol of the formula XI
- 54
- wherein both R1 and R2 represent a silyl protecting group.
A process for preparing an ether of formula XXVI
- 55
- wherein
- R1 is benzyl which is mono- or disubstituted by alkoxy,
- R2 represents a protecting group for a hydroxy group or hydrogen and
- R10 is N-oxazolidinyl which is unsubstituted or substituted by alkyl, benzyl or phenyl;
- ORe wherein Re is alkyl or benzyl, or
- N(Ra)2 wherein Ra is alkyl or benzyl,
- characterized in that a compound of formula XXVII,
- 56
- in which the radicals R2 and R10 are as defined for the compound of formula XXVI, is reacted with a trichloroacetimidate of formula XVII
- 57
- wherein m is 1 or 2, in the presence of samarium triflate or ytterbium triflate, and afterwards, if desired, the protecting group R2 is split off.
9 more elements
Dependencies are inferred from the claim text.