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Biotage® MP-TsOH

Rapid Purification of Amines by Catch and Release, Solvent Exchange

mp-tsoh

Biotage® MP-TsOH resin is a sulfonated macroporous polystyrene resin and has been optimized for use as a bound reagent or scavenger resin for the synthesis of small molecules.The sulfonic acid groups in MP-TsOH are readily accessible for removal of basic compounds (e.g. primary, secondary, and tertiary amines) by quaternary salt formation.

CONSUMABLES

Part No. Description Product type Pack Size Price
800461 MP-TsOH, 10 g Consumables 1 Log in for price
800462 MP-TsOH, 25 g Consumables 1 Log in for price
800463 MP-TsOH, 100 g Consumables 1 Log in for price
800464 MP-TsOH, 1 kg Consumables 1 Log in for price
800498 MP-TsOH, 3 g Consumables 1 Log in for price

Committed to preserving our shared environment – further details available on request.

Can be used in processes in compliance with cGMP standards.

Manufacture of consumables is accredited by the world renowned British Standards Institute.

Flexible supply chains, back up manufacturing and warehousing ensures supply risk reduction

Can be used in processes in compliance with GLP standards.

Products which are scaleable from lab or development to process scale.

Long to indefinite product shelf life, reduced process risk.

Supports pharma guidelines for reducing elemental impurities in APIs.

Further extractable information provided on request.

Raw materials certified free of materials of human or animal origin.

Chemical substances used in our manufacturing process do not require registration.

Able to withstand mechanical stirring and heating under normal reaction conditions.

Download the product note.

 

Background

Biotage® MP-TsOH resin is a sulfonated macroporous polystyrene resin and has been optimized for use as a bound reagent or scavenger resin for the synthesis of small molecules. The sulfonic acid groups in MP-TsOH are readily accessible for removal of basic compounds (e.g. primary, secondary, and tertiary amines) by quaternary salt formation.

Catch-and-Release Purification of Amines /Solvent Exchange

The procedure for isolating amines using MP-TsOH in columns is known as catch-and-release and is detailed below. When a solution containing an amine is passed through a MP-TsOH column the amine is retained or “caught” by the resin. Non-basic impurities are not retained and are further removed by washing the column with an organic solvent, such as DCM, THF or methanol. The product is subsequently “released” from the column by elution with a solution of ammonia in methanol. Amine salts of weak conjugate acids (e.g. acetate and trifluoroacetate) are exchanged onto the resin and are released as the free amine during the ammonia/methanol wash.

This approach has also proven itself to be effective for the fast, room temperature removal of high boiling point solvents from a solution of product. Basic product caught on the resin can be washed free of solvents such as DMSO, or DMF, by simple washing techniques. They are isolated by releasing with volatile alternatives such as methanolic ammonia / THF or MeOH.

Catch-and-Release Procedure

  1. Column Pre-conditioning: Wash the column with DCM, methanol or THF (4 mL/g resin).
  2. Sample Loading: Load the amine sample or reaction mixture onto column under gravity and discard the eluent.
  3. Wash Impurity: Remove the non-basic impurities by washing with DCM (3 x 3mL/g resin). Discard the wash.
  4. Amine Elution: Elute basic amines with a solution of ammonia in methanol (2 M, 4 mL/g resin). Evaluate the use of 4 M ammonia/methanol solution (2 mL/g resin) to improve elution efficiency and reduce elution volume. Collect the eluent. Wash with methanol (2 x 4 mL/g resin) for complete recovery of the amine.

Application in Reductive Amination Reactions

The reductive amination of carbonyl compounds is widely used in amine synthesis. MP-TsOH(columns can be used to simplify the purification process following this type of reaction. When using this approach, the stoichiometry of the reaction is usually adjusted towards excess carbonyl compound (10–20%) to drive the reaction to completion. It is therefore best suited for reactions where product over-alkylation is not an issue. The catch-and-release purification approach is particularly useful when used in conjunction with a bound reducing agent, such as MP-Cyanoborohydride.

An example of this approach is provided by the synthesis of N-cyclopentylpiperidine (Scheme 1). Reductive amination of 1.2 equivalents of cyclopentanone with 1 equivalent of piperidine was carried out with MP-Cyanoborohydride in 10% (v/v) acetic acid/THF. On completion, the reaction mixture was filtered and the filtrate passed through a conditioned MP-TsOH(column to retain the amine product. The excess carbonyl compound and its reduced product passed directly through the column, with an additional DCM wash removing any remaining non-basic impurities. The free amine was “released” with ammonia/ methanol to afford the product in 76% yield and 97% purity. In addition to product purification, the process serves to exchange the product solution from acetic acid/THF to a more volatile ammonia/methanol solution.

Other Applications

In Mitsunobu, Suzuki and Heck reactions, it is often challenging to isolate pure products from the by-products such as triphenylphosphine oxide and palladium. MP-TsOH columns can be used to purify these products when they contain a basic functional group. The reaction mixture is applied to the column and the product is retained by MP-TsOH. The byproducts can be easily removed with a methanol or DCM wash step. The product can then be released by eluting with 2 M ammonia in methanol. MP-TsOH may also be used in cartridge applications to perform Catch-and-Release of amine derivatives in analogy to silica-derived SCX columns.