US 7,417,153 B2Granted

Method for the production of 3-amino-5-(hydroxymethyl)cyclopentane-1,2-diol derivatives

AssigneeLonza Ltd.

InventorsGareth-John Griffiths, Silvia Lange, Walter Brieden

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Abstract

A method for the production of acetals and ketals of 3-amino-5-(hydroxymethyl) cyclopenlane-1,2-diols of formula (I): (and/or the enantiomer), where R1 is H, C1-6-alkyl, C3-8-cycloalkyl or benzyl and (i) R2 is methyl and R3 is ethyl, (ii) R2 is H and R3 is C1-6-alkyl or phenyl or (iii) R2 and R3 together form a group of formula —(CH2)n— with n=4 to 6, present as free amines or as salts of di- or tri-basic organic acids, starting from 2-acetyl-2-aza-bicyclo[2.2.1]hept-5-en-3-one of formula (II): (and/or the enantiomer). The method is equally useful, depending on the starting material, for the production of enantiomerically-pure compounds, or mixtures with arbitrary enantiomeric content.

A method for preparing a compound of formula:

and/or mirror image thereof,
wherein R1 is hydrogen, C1-6-alkyl, C3-8-cycloalkyl or benzyl, and in which (i) R2 is methyl and R3 is ethyl, or (ii) R2 is hydrogen and R3 is C1-6-alkyl or phenyl, or (iii) R2 is methyl and R3 is methyl, or (iv) R2 and R3 together are a group of the formula —(CH2)n— with n=4 to 6, and which is in the form of a free amine or a salt of a dibasic or tribasic organic acid, comprising:
(A) converting a 2-acetyl-2-azabicyclo[2.2.1]hept-5-en-3-one of formula:
and/or mirror image thereof,
by cis hydroxylation of the double bond into a 2-acetyl-5,6-dihydroxy-2-azabicyclo[2.2.1]heptan-3-one of formula:
and/or mirror image thereof,
(B) converting the compound of the formula III by reaction with a ketone or an aldehyde of the formula R2—CO—R3, wherein R2 and R3 have the above stated meanings, or by reaction with 2,2-dimethoxypropane or 2,2-dimethoxybutane into a ketal or an acetal of formula:
and/or mirror image thereof,
wherein R2 and R3 have the above stated meanings,
(C) converting the ketal or acetal of the formula IV by reductive ring opening into a compound of formula:
and/or mirror image thereof,
wherein R2 and R3 have the above stated meanings,
(D) optionally converting the compound of formula V or an alcoholate thereof by reaction with dimethyl sulfate, benzyl chloride or a halide of the formula R1—X wherein R1 has the above stated meaning other than hydrogen, and X is bromine or iodine, into an ether of formula:
and/or mirror image thereof,
wherein R1 has the above stated meaning other than hydrogen and R2 and R3 have the above stated meanings,
(E) converting a compound of the formula V or VI by alkaline hydrolysis into a compound of formula:
and/or mirror image thereof,
wherein R1, R2 and R3 have the above stated meanings, and
(F) optionally converting the compound of the formula I by addition of a dibasic or tribasic organic acid into corresponding salt wherein R1, R2 and R3 have the above stated meanings.

16 more elements

Facts

Application

10/584,848Filed 24 Jan 2005

Priority

EP 0400205530 Jan 2004

Published

US 2007/0043225 A122 Feb 2007

Granted

26 Aug 2008

Term ends

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Classification5 codes

C07D 317/44
Having the hetero atoms in positions 1 and 3: ortho- or peri-condensed with carbocyclic rings or ring systems
C07D 209/52
Condensed with one carbocyclic ring: condensed with a ring other than six-membered
C07D 419/08
Containing two hetero rings: linked by a carbon chain containing alicyclic rings
C07D 491/08
In which the condensed system contains two hetero rings: bridged systems

Abstract

Claims32