Ethylene Glycol → 1007853-28-2

Participants

Reaction Steps

To a solution of 8-hydroxyquinoline-5-carbaldehyde (A,Oakwood Products) in ethylene glycol, p-TsOH is added to form 5-(1,3-dioxolan-2-yl)quinolin-8-ol (B). After purification, 5-(1,3-dioxolan-2-yl)quinolin-8-ol is added to a solution of MeI and NaH in THF to give C. A solution of C in THF is added to 1 eq of the Grignard reagent formed from magnesium turnings and L-N-Boc-2-bromomethyl glycine allyl ester (Advanced Technology & Industrial Co., Ltd., Hong Kong) at 0° C.; the reaction mixture is monitored by TLC until allyl(S)-vinyl 2-(tert-butoxycarbonylamino)-3-(5-formyl-8-methoxyquinolin-2-yl)propanoate (D) is formed. The reaction mixture is quenched with aqueous acetic acid, and purified by flash chromatography. The O-methyl and N-t-BOC protecting groups are simultaneously removed by treatment of D with warm 48% HBr/HOAc. The freed aliphatic amino group is protected as a fluorenoxymethylenecarbonyl carbamate, followed by condensation of the benzaldehyde moiety with two equivalents of 4-fluororesorcinol in methanesulfonic acid at rt. The resulting pro-fluorophore G is isolated by precipitation from water and filtration, followed by dehydrogenative oxidation with p-choranil in methane/chloroform. The resulting dye H is purified by flash chromatography using methanol in chloroform as eluant, and then readied for peptide synthesis of allyl ester deprotection using sodium 2-ethylhexanoate and catalytic Pd(PPh3)4 in ethyl acetate and dichloromethane to give compound I.

Provenance & Evidence