C-X-Y-Fragment Nitrile Oxide on Solid Phase

Attachment of the tetrahydropyranyl linker. Polystyrene carboxyHc add resin (Novabiochem, 15 g, 1.24 mmol g , 18.6 mmol) was gently agitated for 16 h with 2-aminomethyl-3,4-dihydro-2H-pyrane (4.2 g, 37 mmol), in the presence of HOBT (12.5 g, 81 mmol) and DCC (16.9 g, 81 mmol) in DMF (100 mL). The product was washed as follows  

Immobilization of the nitroethanol A solution of nitroethanol (8.7 g, 93 mmol) in CH2CI2 (150 mL) was added to the resin and the suspension was stirred gently for 24 h. The resin (263) was washed as follows  

The resin was desiccated and dispensed into the ACT 495 block (100 mg/ well, calculated loading 1.01 mmol g ). 

Cycloaddition 1 m DMF solutions of PhNCO (20 equiv.), EtsN (20 equiv.), and alkyne (10 equiv.) were sequentially added to the reaction chambers. The reactions were agitated at 50 °C for 5 h. The resin (265) was washed as follows  

Cleavage 20% TFA in CH2CI2 was dispensed and the reaction block was stirred for 30 min. The product solutions were collected by filtration into a 96-well plate and evaporated to dryness in a speed-vac. 

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