Benzyl-Linked Approaches for Secondary Amines

Attachment of a secondary amine as starting material to the chlorobenzyl group 

Cleavage of N-bmzyl-linked tertiary amines fi om a support with a-chloroetliyl chlorofomiate/MeOH to yield secondary amines 6 An excess of an amine was first coupled to Merrifield resin suspended in DMF (if the amine was added as a hydrochloride, then 20 equiv. of DIPEA was added). The mixture was stirred for 17 h at 50 °C. The substitution level was found to be 0.6 mmol ( 85%). To a suspension of the resin in 1,2-dichloropro-pane, 10 equiv. of a-chloroefhyl chloro formate was added and the suspension was stirred for 3 h at rt. The resin was then filtered off and fhe filtrate was concentrated to dryness. The residue was redissolved in MeOH and the solution was refluxed for 3 h. Evaporation of the volatiles yielded the secondary amine 6 as its hydrochloride. The isolated yield varied from 70% to 95 %, depending on the type of amine. 

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