Sodium Hydroxide → 5-Bromothiophene 2-Oxoacetic Acid

Ethyl 2-(5-bromothien-2-yl)glyoxalate (45.6 g, 173 mmol) from Step A was dissolved in a mixture of 100 mL THF, 100 mL methanol, and 300 mL water, then treated with 10 N NaOH (26 ml, 260 mmol) at room temperature for 20 hours. Volatile solvents were removed by rotary evaporation. The residue was dissolved in 2 L water and extracted with diethyl ether (250 mL). The aqueous layer was acidified to pH 1 with 6 N HCl, and extracted with diethyl ether (3×300 mL). The combined diethyl ether extracts were dried over Na2SO4 and concentrated in vacuo to yield 2-(5-bromothien-2-yl)glyoxalic acid, Intermediate 1 (38.7 g, 95%). The product was then recrystallized from diethyl ether. m.p. 119-120° C.; MS (M−H) 235.1; 1H NMR (300 MHz, CDCl3) d 9.00 (1H, br s), 8.15 (1H, d, J=4.2 Hz), 7.16 (1H, d, J=4.2 Hz); 13C NMR (75 MHz, CDCl3) d 173.80, 159.58, 140.14, 137.17, 132.58, 130.48; IR (KBr) 3326, 3124, 1756, 1634, 1415, 1363, 1308, 1253cm−1;

1. customVolatile solvents were removed by rotary evaporation
2. dissolutionThe residue was dissolved in 2 L water
3. extractionextracted with diethyl ether (250 mL)
4. extractionextracted with diethyl ether (3×300 mL)
5. dry with materialThe combined diethyl ether extracts were dried over Na2SO4
6. concentrationconcentrated in vacuo

ORD record

ord-a4950dd324504cfea3ecbf55a917da09

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07846671B2