methyl 6-azidohexanoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: AHA was synthesized following a reported method with modifications. To methyl 6-azidohexanoate (3.4 g, 20 mmol) in 20 ml of mixture of MeOH/H2O (4/1 v/v) LiOH (2.5 g, 60 mmol) was added. After being stirred for 5 h at room temperature, the reaction mixture was poured into brine and washed with hexane to remove unreacted Ester. The aqueous fraction was acidified with HCl, extracted with ethyl acetate. Combined organic fractions were washed with brine and died over MgSO4. Ethyl acetate was removed under reduced pressure that resulted to transparent liquid. Yield 93%. AHA was synthesized washed with hexane to remove unreacted Ester extracted with ethyl acetate Combined organic fractions were washed with brine Ethyl acetate was removed under reduced pressure that resulted to transparent liquid

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 6-azidohexanoate was synthesized via a modified literature procedure. A reaction mixture of methyl 6-bromohexanoate (6 g, 29 mmol) and NaN3 (9.4 g, 144 mmol) in 30 ml of DMF was stirred at 75° C. for 14 h under N2. After cooling down, the reaction mixture was poured into water. The product was extracted with hexane, washed with brine, and dried under MgSO4. Solvent was evaporated to give transparent liquid. Yield: 95%. After cooling down The product was extracted with hexane washed with brine dried under MgSO4 Solvent was evaporated to give transparent liquid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 6-bromohexanoate was reacted with sodium azide to give methyl 6-azidohexanoate, then converted to the corresponding hydrazide using hydrazine hydrate. The linker compound 6-azidohexanehydrazide was conjugated with DOX hydrochloride in dry methanol, with a drop of acetic acid, forming the desired DOX-azide compound. The one-pot method polymerization/click method shown in the scheme was used to synthesize the new DOX-polyMPC copolymer. The polymer was characterized with NMR spectroscopy and GPC, while drug weight percent was measured using a UV method.