Sodium Chloride → HCID 118276890, compound

Participants

Reaction Steps

Variant B: Adapting literature known protocols (Krapcho, Synthesis, 1982, 805-822 & 893-914; and Stowe, et al., Org. Lett., 2010, 12(4), 756-759), a solution of trimethyl 2-(5-chloro-2-nitro-phenyl)propane-1,1,3-tricarboxylate (18b′) (3.74 g, 10.0 mol) and sodium chloride (NaCl) (292 mg, 5.0 mmol) in a mixture of dimethylsulfoxide (DMSO) (23 mL) and water (780 μL) is heated to reflux for about 12 h. The reaction is monitored by TLC and/or analytical LC/MS to completion. Aqueous work-up and purification by silica gel column chromatography using ethyl acetate (EtOAc) and hexanes mixtures afford dimethyl 3-(5-chloro-2-nitro-phenyl)pentanedioate (18b″). Adapting literature known protocols (Nejman, et al., Tetrahedron, 2005, 61, 8536-854), 3-(5-chloro-2-nitro-phenyl)pentanedioic acid (18b) is prepared heating a solution of dimethyl 3-(5-chloro-2-nitro-phenyl)pentanedioate (18b″) (3.16 g, 10.0 mmol) in a mixture of 6.0 M hydrochloric acid (HCl) and 1,4-dioxane for about 12 h to reflux (105° C. oil bath temperature) to effect complete ester hydrolysis and decarboxylation. The reaction is monitored by TLC and/or analytical LC/MS to completion. The solvents are distilled off under reduced pressure using a rotary evaporator. Aqueous work-up and purification by crystallization from ethyl acetate (EtOAc) and hexanes mixtures afford the title compound (18b).

Provenance & Evidence