Hydrochloric Acid → HCID 89473318, compound

Participants

Reaction Conditions

Reaction Steps

An ice cold solution of 5-(4-fluorobenzyl)-7-methyl-6-oxo-9-(p-tolyl)-1,3,4,5,6,7-hexahydropyrano[3′,4′:4,5]pyrrolo[2,3-c]pyridine-8-carbaldehyde (150 mg, 0.348 mmol) and Zinc iodide (86 mg, 0.697 mmol) in Dichloromethane (DCM) (1783 μl) was treated with TMS-CN (909 μl, 3.48 mmol) dropwise. After 30 min, the reaction mixture was quenched with a 10% solution of Na2S2O3. DCM was added and the layers were partitioned. The organic layer was washed with brine, dried (Na2SO4), filtered and concentrated. The residue was dissolved in MeOH (3 mL), cooled to 0° C. and treated dropwise with 1M HCl in 1,4-dioxane (697 μl, 0.697 mmol). After 1 h, the reaction mixture was concentrated in vacuo. The residue was then dissolved in DCM (3 mL) and treated with DHP (96 μl, 1.045 mmol) and PPTS (4.38 mg, 0.017 mmol). After 45 min, Et3N (0.5 mL) was added and the reaction mixture was poured into sat. aq. NaHCO3. EtOAc was added and the layers partitioned. The organic phase was washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by ISCO (0-50% EtOAc-hexanes) to afford 2-(5-(4-fluorobenzyl)-7-methyl-6-oxo-9-(p-tolyl)-1,3,4,5,6,7-hexahydropyrano[3′,4′:4,5]pyrrolo[2,3-c]pyridin-8-yl)-2-((tetrahydro-2H-pyran-2-yl)oxy)acetonitrile (170 mg, 0.314 mmol, 90% yield) as a white foam. LCMS (m/z) ES+=542 (M+1).

Provenance & Evidence