Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Mixing of two or more solid polymers; mixing of solid...
Reexamination Certificate
2002-11-12
2004-12-07
Choi, Ling-Siu (Department: 1713)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Mixing of two or more solid polymers; mixing of solid...
C525S333300, C525S333400
Reexamination Certificate
active
06828389
ABSTRACT:
The invention relates to a process for the preparation of polymer-bound 2-chlorotrityl chloride of the formula
in which the symbol
is a polymeric support and preferably a crosslinked polystyrene resin.
Polymer-bound 2-chlorotrityl chloride is a commercially obtainable (Calbiochem-Novabiochem AG, Läufelfingen, Switzerland, Product No. 01-64-0021) reagent for the solid-phase synthesis of peptides. It is reacted here firstly with an N-protected amino acid, which forms the C-terminus of the peptide to be synthesized, to give the corresponding trityl ester. After synthesis of the peptide chain, the peptide is cleaved by treatment with a carboxylic acid, for example dilute trifluoroacetic acid or acetic acid, the corresponding polymer-bound trityl ester of the formula
in which R is a C
1-4
-alkyl or C
1-4
-haloalkyl group and preferably methyl or trifluoromethyl being formed. The resin is thus consumed and can no longer be employed for further syntheses in this form.
C
1-4
-Alkyl is to be understood here and below as meaning all alkyl groups having 1 to 4 carbon atoms, that is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl. C
1-4
-Haloalkyl is correspondingly to be understood as meaning all C
1-4
-alkyl groups having one or more identical or different halogen atoms as substituents, preferably perfluorinated C
1-4
-alkyl groups such as trifluoromethyl.
The object of the present invention was therefore to make available a process which regenerates the polymer-bound 2-chlorotrityl chloride again from the acyloxylated resin (II) formed after cleavage of the peptide, which can then be used again for peptide syntheses.
According to the invention, this object is achieved by the process according to the invention.
It has been found that by simple treatment of the acyloxylated resin (II) with hydrogen chloride in an organic solvent the polymer-bound 2-chlorotrityl chloride (I) can be regenerated. Since the replacement of carboxylate by chloride is obviously an equilibrium reaction, the treatment is advantageously repeated a number of times using fresh solvent in order to remove the released carboxylic acid from the system and thus to achieve a complete replacement. It is also possible to percolate a packing of the acyloxylated resin (II) with a solution of hydrogen chloride until the carboxylate is completely replaced by chloride.
A suitable solvent is fundamentally any anhydrous organic solvent which does not react with hydrogen chloride and has an adequate solvent power for this. Preferably, dichloromethane is employed as the solvent.
The process according to the invention can be carried out both using a prepared solution of hydrogen chloride and using a solution produced in situ by passing gaseous hydrogen chloride into a reactor charged with the solvent and the acyloxylated resin (II).
The following example clarifies the implementation of the process according to the invention, without a restriction being seen therein.
REFERENCES:
patent: 4346187 (1982-08-01), Nichols
patent: 5198531 (1993-03-01), Webber et al.
patent: 5563220 (1996-10-01), Webber et al.
patent: 92-22591 (1992-12-01), None
Harre et al., “An efficient method for activation and recyclingof trityl resins”, Reactive & Functional Polymers. 41, 111-114(1999).*
Copy of International Search Report from applicants's corresponding International (PCT) application.
Patent Abstracts of Japan, vol. 199, No. 612, (Dec. 26, 1996).
Patent Abstracts of Japan, vol. 011, No. 246 (C-439), (Aug. 11, 1987).
Choi Ling-Siu
Fisher Christen & Sabol
Lonza AG
LandOfFree
Method for producing polymer-bonded 2-chlorotrityl-chloride 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 for producing polymer-bonded 2-chlorotrityl-chloride, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for producing polymer-bonded 2-chlorotrityl-chloride will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3273059