Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Patent
1995-07-18
1998-04-28
Daus, Donald G.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
548232, 564336, 564355, 564473, C07D26320
Patent
active
057446300
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to efficient processes for producing an 3-amino-2-hydroxy-1-propanol derivative of the following general formula (2) and an oxazolidinone derivative of the following general formula (5), both of which are of value as intermediates for the production of medicines. ##STR2## wherein R.sup.1 represents alkyl, aralkyl or aryl; R.sup.2 and R.sup.3 independently represent hydrogen or an amino-protecting group; provided, however, that both R.sup.2 and R.sup.3 are not concurrently hydrogen.
In particular, optically active 3-amino-2-hydroxy-1-propanol derivatives and oxazolidinone derivatives derived therefrom are of value as intermediates for the production of the HIV protease inhibitor.
PRIOR ART
The following processes are already known for the production of 3-amino-2-hydroxy-1-propanol derivatives of general formula (2) and oxazolidinone derivatives of general formula (5) which are derivable therefrom. involving formation of an azide compound (Bulletin de la Societe Chimique de France, 129, 585, 1992). coupling reaction in the presence of vanadium trichloride and zinc (Tetrahedron 48, 2069, 1992). N-(benzyloxycarbonyl)allylamine derivative (Tetrahedron Letters 25, 5079, 1984).
However, among the above processes, the first-mentioned process (A) utilizing the azide compound has the disadvantage that it requires not only costly reagents but also many processing steps. The third-mentioned process (C) utilizing an N-(benzyloxycarbonyl)allylamine also requires expensive reagents and many processing steps. The second process (B) utilizing vanadium trichloride involves a comparatively short reaction procedure but is disadvantageous in that the indispensable reducing agent vanadium trichloride is comparatively expensive and that when applied to N-tosylvarinal which is the exclusive compound described in the examples of synthesis of 3-amino-2-hydroxy-1-propanol derivatives, the process hardly provides for stereoselectivity.
Thus, the processes thus far known have many disadvantages to be overcome for commercial production of 3-amino-2-hydroxy-1-propanol derivatives or oxazolidinone derivatives derivable therefrom, thus being neither efficient nor economical for commercial application.
DISCLOSURE OF THE INVENTION
Developed in view of the above state of the art, it is an object of the present invention to provide an efficient and economical method for producing 3-amino-2-hydroxy-1-propanol derivatives and oxazolidinone derivatives derivable therefrom.
After intensive research, the inventors of the present invention found that as an aminoaldehyde derivative whose amino group has been protected and a formaldehyde source compound are subjected to hetero-coupling reaction with the aid of a low valence titanium, the objective 3-amino-2-hydroxy-1-propanol derivative can be obtained in a short sequence of steps and that where the amino-protecting group of said aminoaldehyde derivative is an ester residue such as benzyloxycarbonyl or t-butoxycarbonyl, a 4-substituted-5-hydroxymethyloxazolidinone derivative can be obtained by treating said coupling reaction product further with a base. The present invention has been developed on the basis of the above findings.
The present invention, therefore, is directed, in a first aspect, to a process for producing an 3-amino-2-hydroxy-1-propanol derivative of general formula (2): ##STR3## (wherein R.sup.1, R.sup.2 and R.sup.3 are as defined below) which comprises reacting an aminoaldehyde derivative of general formula (1): ##STR4## (wherein R.sup.1 represents alkyl, aralkyl or aryl; R.sup.2 and R.sup.3 independently represent hydrogen or an amino-protective group; provided, however, that both R.sup.2 and R.sup.3 are not concurrently hydrogen) by hetero-coupling reaction with a formaldehyde source in the presence of a low valence titanium.
The present invention is further directed, in a second aspect, to a process for producing an oxazolidinone derivative of general formula (5): ##STR5## (wherein R.sup.1 is as defined hereinbefore) which compr
REFERENCES:
patent: 4219508 (1980-08-01), Wagner
patent: 4933511 (1990-06-01), Gredley et al.
patent: 5220020 (1993-06-01), Buchwald et al.
patent: 5367094 (1994-11-01), Chung
patent: 5399763 (1995-03-01), Satoh et al.
patent: 5556516 (1996-09-01), Koyama
patent: 5659065 (1997-08-01), Goschke
Park et al., Practical Hydroxymethylation of Aldehydes and Ketones via Pinacol Cross-Coupling Reactions with Paraformaldehyde, Tetrahedron, vol. 48, No. 11, 1992, pp. 2069-2080.
Awaji Hiroshi
Inoue Kenji
Takahashi Satomi
Daus Donald G.
Kaneka Corporation
LandOfFree
Method of producing 3-amino-2-hydroxy-1-propanol derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method of producing 3-amino-2-hydroxy-1-propanol derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of producing 3-amino-2-hydroxy-1-propanol derivatives will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1533151