Hydrochloric Acid → 3-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)propanal

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Reaction Steps

To a solution of 5-(2-(1,3-dioxolan-2-yl)ethyl)-4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridine (0.520 g, 1.28 mmol) in THF (4.2 mL) was added aqueous HCl (6 M, 0.639 mL, 3.83 mmol). The reaction mixture was stirred at ambient temperature for about 2 h and was heated to about 50° C. for about 1 h. The reaction was cooled to ambient temperature and water (0.64 mL) was added and the reaction stirred for about 16 h. The pH was adjusted to about 7 with saturated aqueous NaHCO3 and EtOAc (about 10 mL) was added. The layers were separated and the aqueous phase was extracted with EtOAc (10 mL). The combined organics were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. Acetone (12 mL) and pyridinium p-toluenesulfonate (0.096 g, 0.383 mmol) were added. The reaction was heated at reflux for about 2 h. The reaction was cooled to ambient temperature and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 0-50% EtOAc in DCM to give 3-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)propanal (0.44 g, 84%, 90% purity) as an off white foam: LC/MS (Table 1, Method b) Rt=2.50 min; MS m/z: 363 (M+H)+.

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