Salicylaldehyde → m-PEG4-benzaldehyde

Participants

Reaction Steps

The bisacrylamide triethylene glycol acetal crosslinker (606) or triglyme crosslinker as shown in FIG. 6 was synthesized in four steps on a multigram scale. The first step involved the preparation of 1-chloro-3,6,9-trioxadecane (603) using the procedure of Loth, H. & Ulrich, F. (1998) J. Control Release. 54, 273. Compound 603 was then used to alkylate hydroxy benzaldehyde (605) and produce p-(1,4,7,10-Tetraoxaundecyl)benzaldehyde (604). Compound 603 was chosen as the alkylating agent since it can be easily synthesized on a large scale (100 grams) enabling the preparation of 4 on a 20 gram scale (70% yield), using potassium carbonate as the base and 18-crown-6 as the phase transfer catalyst. Hydroxy-benzaldehyde could also be alkylated using 1-tosyl-3,6,9-trioxadecane and 1-bromo-3,6,9-trioxadecane but these approaches were discontinued because significantly lower yields of the desired product were obtained.

Provenance & Evidence