Nitric Acid → 4-Bromo-5-nitro-thiophene-3-carboxylic acid ethyl ester

Temperature

0 °C

4-Bromo-thiophene-3-carboxylic acid ethyl ester (97.6 g, 0.415 mol) was added over 10 min via pipette to 18.0 M sulfuric acid (660 mL) at 0° C. After stirring 5 min at 0° C., fuming nitric acid (18 mL) dissolved in 18.0 M sulfuric acid (130 mL) was added via addition funnel over 30 min. After the addition was completed, the reaction mixture was stirred for 5 min at 0° C., and then was poured onto ice (3.5 kg). The resulting precipitate was collected by filtration and was washed sequentially with water (300 mL), 10% aqueous sodium bicarbonate solution (400 mL) and water (300 mL). The brown/yellow solid thus obtained was dried in a vacuum oven overnight at 40° C. to afford the crude product, 4-bromo-5-nitro-thiophene-3-carboxylic acid ethyl ester (97.9 g, 0.350 mol, 84%). This material was further purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 25% hexanes in dichloromethane) in 20 g portions prior to use in the next step (recovery=80-90%). 1H NMR (400 MHz, DMSO-d6) δ: 1.31 (3H, t, J=7.0 Hz), 4.30 (4H, q, J=7.0 Hz), 8.68 (1H, s).

1. additionwas added via addition funnel over 30 min
2. additionAfter the addition
3. stirringthe reaction mixture was stirred for 5 min at 0° C.
4. additionwas poured onto ice (3.5 kg)
5. filtrationThe resulting precipitate was collected by filtration
6. washwas washed sequentially with water (300 mL), 10% aqueous sodium bicarbonate solution (400 mL) and water (300 mL)
7. customThe brown/yellow solid thus obtained
8. customwas dried in a vacuum oven overnight at 40° C.

ORD record

ord-5eb0a97806ad411cb5d5b0bcde7aee8d

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08097613B2