Ethyl bromoacetate → Ethyl 2-((3-(1,3-dioxolan-2-yl)quinolin-6-yl)oxy)acetate

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Reaction Steps

The masked aldehyde 3-(1,3-dioxolan-2-yl)-quinolin-6-ol LPO 55016 was obtained via a similar method as for SSA 48104 from 2-chloro-6-hydroxyquinoline-3-carbaldehyde LPO 50188A. LPO 50188A itself was prepared by treatment of 2-chloro-6-methoxyquinoline-3-carbaldehyde by boron tribromide (BBr3) in dichloromethane. Finally quinolin-6-ol LPO 55016 was O-alkylated by treatment with ethyl 2-bromoacetate and cesium carbonate as a base in acetone for 2 hours at 85° C. to yield ethyl 2-((3-(1,3-dioxolan-2-yl)quinolin-6-yl)oxy)acetate LPO 55070A (reaction scheme 2). The masked aldehyde 3-(1,3-dioxolan-2-yl)-8-(trifluoromethyl)quinolin-5-ol LPO 50180C was prepared by radical trifluoromethylation of dioxolane TTA 46034 using a methodology developed by Langlois B. et al., Tetrahedron Lett., (32), 51, 7525-7528, 1991 and modified by Baran P. et al., PNAS, 108, 35, 14411-14415, 2011 (reaction scheme 2).

Provenance & Evidence