Water → 1-[1-(2,4-difluorobenzyl)-3-({[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl]ethanone

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 3-(chloromethyl)-1-(2,4-difluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate (3 mL, 0.197M in CH2Cl2, 0.591 mmol) [prepared as described in step 2 of example 40] in anhydrous DMF (5 mL) was added (R)-(−)-2,2-dimethyl-1,3-dioxolane-4-methanol (2.955 mmol, 0.37 mL, 5.0 eq.) followed by i-Pr2NEt (0.407 g, 3.14 mmol, 0.55 mL, 4 eq.). The mixture, under nitrogen, was placed in an oil bath and the bath was warmed to 40° C. After stirring for 24 hours (40° C.) the reaction was judged to be complete by HPLC-MS analysis. Water (0.5 mL) was added and after 45 minutes the volatiles were removed in vacuo (ca. 2 torr) to give a golden yellow oil. The crude material was purified by chromatography on a column of silica gel (40 mm OD, 100 g, 230-400 mesh, packed with CH2Cl2, eluted with CH2Cl2-EtOAc 70:30 v/v, 1.0 L, 1.0 L, 25 mL fractions) using the flash technique. Fractions were combined to afford 0.224 g (85%) of 1-[1-(2,4-difluorobenzyl)-3-({[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy)methyl)-1H-pyrrolo[2,3-c]pyridin-5-yl]ethanone as a colorless oil. TLC (Merck, CH2Cl2:EtOAc 50:50, UV-+, cerium molybdate-+): Rf=0.26. LC-MS (Eclipse XDB-C8, 0.8 mL/min, gradient 80:20 to 5:95H2O (+0.1% HOAc):CH3CN—5 minutes, APCI, +mode): RT—3.456 min, m/e=447.20 (M+H+, base).

Provenance & Evidence