Sulfuric Acid → HCID 178469183, compound

Participants

Reaction Conditions

Reaction Steps

To solution of ethyl 4-amino-1-(3,4-difluorobenzyl)-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (6 g, 14.8 mmol) in 1,4-dioxane (16 mL) at 0° C. was added dropwise a cold solution of sulfuric acid (16 mL, 300 mmol) in water (24 mL) followed by dropwise addition of a solution of sodium nitrite (4.2 g, 60.5 mmol) in water (12 mL) in 10 min. After stirring for 1 h at 0° C. and 3 h at RT for 3 h the mixture was cooled to 0° C. and more sodium nitrite (1.3 g) in water (3 mL) was added. After 2 h at RT cold water was added and the mixture was filtered washing with water. The solid was dissolved in MeOH and solid NaHCO3 was added. The mixture was stirred for 10 min then filtered and concentrated. The residue was dissolved in EtOAc and washed with saturated NaHCO3/water and the organic phase was dried (Na2SO4), concentrated and dried in vacuo to provide ethyl 1-(3,4-difluorobenzyl)-4-hydroxy-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (5.02 g, 13.8 mmol, 93% yield) as a brown solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.48 (t, J=7 Hz, 3 H), 2.86 (s, 3 H) 4.49 (q, J=7 Hz, 2 H), 5.40 (br s, 2 H), 6.66 (d, J=3.51 Hz, 1 H), 6.91-7.15 (m, 4 H), 12.82 (br s, 1 H); LCMS (m/z) ES+=347 (M+1).

Provenance & Evidence