4-Chloro-3-Fluorobenzaldehyde → 6-chloro-7-fluoro-1H-indole

Participants

Reaction Conditions

Reaction Steps

Methyl 2-azido-3-(4-chloro-3-fluorophenyl)propenoate Sodium (2.32 g, 100 mmol) was added portionwise to stirred methanol (200 mL) at 0° C. under Ar. The mixture was stirred for 1 h and cooled to −15° C. A solution of 4-chloro-3-fluorobenzaldehyde (4.0 g, 25 mmol), methyl azidoacetate (8.7 g, 75 mmol) in methanol (20 mL) was added. The mixture was stirred for 3 h, warmed to 4° C. and stirred for 16 h and partitioned between water (300 mL) and ether (3×200 mL). The organic extracts were combined and washed with brine (2×), dried (magnesium sulfate) and concentrated in vacuo to give an orange solid. Recrystallisation (methanol) gave the product (5.09 g, 80% yield) as a pale yellow solid: IR νmax (Nujol)/cm−1 2115, 1708, 1616, 1234, 1060, 896, 818 and 616; NMR δH (400 MHz, CDCl3) 3.82 (3H, s) 6.64 (1H, s) 7.35-7.46 (2H, m) 7.74-7.78 (1H, m).

Provenance & Evidence