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Biotage® PS-TBD

Powerful Non-nucleophilic Guanidine Base for Alkyation and C-C Bond Formation

PS-TBD

Biotage® PS-TBD is a polymer-supported bicyclic guanidine moiety (1,5,7-triazabicyclo[4.4.0]dec-5-ene) base. PS-TBD applications include alkylation of phenols and amines; esterification of carboxylic acids using alkyl halides; alkylation of activated methylene compounds; de-halogenation of organic halides; high throughput synthesis of aryl triflates and aryl nonaflates, and the regioselective synthesis of lysophospholipids.

CONSUMABLES

Part No. Description Product type Pack Size Price
800421 Biotage® PS-TBD, 10 g Consumables 1 Log in for price
800422 Biotage® PS-TBD, 25 g Consumables 1 Log in for price
800423 Biotage® PS-TBD, 100 g Consumables 1 Log in for price
800424 Biotage® PS-TBD, 1 kg Consumables 1 Log in for price
800513 Biotage® PS-TBD, 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

The Williamson ether synthesis was discovered in the mid-19th Century and to date it remains one of the best ways to synthesize unsymmetrical ethers. The original conditions were harsh and required prolonged heating in basic environments. Recent modifications for reactions below 100 °C, involve addition of alkyl derivatives of Brönsted acids, such as alkyl sulfates. Not only is the removal of salt following the reaction involve an additional step, which may be problematic, but these are often carcinogenic and pose health and safety issues at scale.

PS-TBD resin can facilitate Williamson ether synthesis at room temperature using very mild conditions, as it is effective at deprotonating moderately acidic hydrogen (up to pKa ca 13). The resin may also be used for the N-alkylation of aryl halides, esterification of carboxylic acids, and alkylation of acidic methylenes.

PS-TBD is stable under bench conditions and can be dispensed using standard laboratory tools (spatulas, Biotage Argoscoop). The resin may be stored at room temperature for extended periods.

Representative Procedures

Synthesis of Tertiary Amines by Reaction of Secondary Amines with Activated Alkyl Bromides

A series of tertiary amines was synthesized by reaction of secondary amines with activated alkyl bromides in the presence of PS-TBD (Scheme 2).

The amine was used in slight excess (1.1 equiv.) of the alkyl bromide and best results were obtained with 2.5 equivalents of PS-TBD. The choice of solvent and temperature of the reaction was found to be important, with optimal conditions provided by THF at 50 °C or MeCN at room temperature. Complete conversion of the alkyl bromide occurred in 16 h to afford a mixture of the desired tertiary amine and residual secondary amine (ca. 0.1 equiv.) The excess secondary amine was selectively scavenged from the mixture by the addition of MP-Isocyanate (a macroporous scavenger for amines) and subsequent stirring at room temperature. MP-Isocyanate was used because of its high reactivity in MeCN. Filtration and concentration afforded the desired tertiary amines as homogeneous products in good-to excellent yields.

While the conditions for the synthesis of the amines may be generalized for certain substructures, the effect of the substrates needs to be considered. For example, the reaction of dibutylamine with both ethyl α-bromoacetate and 4´-bromobenzyl bromide afforded higher yields in MeCN at room temperature than in THF at elevated temperatures (71% vs. 30% and 70% vs. 60%, respectively). The low yield and high purity in THF may be due to loss of the volatile amine at elevated temperatures in conjunction with reaction of the resultant excess alkyl bromide with the resin to form a bound quaternary salt. In contrast, the reaction of indole-3-carboxaldehyde with 4-bromobenzyl bromide afforded higher yields in THF at 50 °C than in MeCN (90% vs. 33%). For further information please see product note PPS382.