Water → Methanol

Participants

Reaction Steps

Methyl 1-(4-chloro-2-fluorobenzyl)-6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (250 mg, 0.591 mmol) was dissolved in THF (2 ml). LiAlH4 (2.53 ml, 2.53 mmol) was added to the mixture at 0° C. and allowed to warm to room temperature. The reaction was stirred for 18 hours at room temperature. The reaction was stopped by the addition of 0.1 mL of water followed by a 10 minute wait, then the addition of a 15% NaOH solution (0.1 mL) followed by a 10 minute wait and finally 0.3 mL of water followed by a 10 minute wait. At this point, a fine powder was formed that was filtered out using Celite™ on a frit. The solution was concentrated in vacuo. The chloro was removed partially by the reduction and the mixture of the two compounds was carried to the next step. (1-(4-chloro-2-fluorobenzyl)-6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)methanol and 1-(2-fluorobenzyl)-6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)methanol (202 mg, 0.512 mmol, 47.8% yield) were isolated together as a yellow oil. The crude mixture was carried for the next step. 1H NMR (400 MHz, CHLOROFORM-d) δ=7.44-7.33 (m, 2 H), 7.32-7.19 (m, 3 H), 7.19-6.91 (m, 4 H), 6.28-6.15 (m, 1 H), 5.55 (s, 1 H), 5.49 (s, 1 H), 4.68 (s, 2 H), 2.81 (d, J=4.0 Hz, 3 H), 2.44 (s, 3 H) LCMS (m/z) ES+=361 (M+1) and LCMS (m/z) ES+=395 (M+1).

Provenance & Evidence