Sulfuric Acid → HCID 68891488, compound

In an oven-dried round bottom flask, 7.0 g of 4-bromo-3-methylbenzoic acid (32.6 mmol) was dissolved in 10 mL of dichloromethane, 30 mL of dimethyl formamide was added to the solution and the resulting mixture was treated with 7.0 mL of oxalyl chloride at 50° C. for 30 min. The reaction mixture was cooled to rt and solvents were removed under reduced pressure. The residual white solids were dissolved in 50 mL of EtOAc and added over 10 minutes to a stirring biphasic system consisting of 150 mL of EtOAc, 150 mL of saturated solution of sodium bicarbonate, and 7.5 g of thiosemicarbazide (81.4 mmol). The resulting reaction mixture was allow to stir at rt for 3 h, organic layer was separated and aqueous was extracted with 2×250 mL of EtOAc. Combined organic extracts were dried over sodium sulfate and concentrated to yield a crude product, contaminated with thiosemicarbazide. This crude material was treated with 25 mL of neat sulfuric acid at rt for 30 minutes. The reaction mixture was diluted with 500 mL of ice-water mixture and basified with solid sodium hydroxide to pH>13, controlling the isotherm by an external ice-bath. The basic heterogeneous solution was extracted 3×300 mL of EtOAc, organic extracts dried over sodium sulfate and concentrated. The crude product was purified by column chromatography using Biotage 40L cartridge (eluant hexanes/EtOAc=1/1) yielding 3.7 g of the title compound: 1H NMR (500 MHZ, CDCl3) δ 2.56 (s, 3H), 5.28 (s, 2H), 7.42 (d, J=6.5, 1H), 7.44 (d, J=6.5, 1H), 7.49 (s, 1H).

1. customsolvents were removed under reduced pressure
2. dissolutionThe residual white solids were dissolved in 50 mL of EtOAc
3. additionadded over 10 minutes to a stirring biphasic system
4. customThe resulting reaction mixture
5. customorganic layer was separated
6. extractionaqueous was extracted with 2×250 mL of EtOAc
7. dry with materialCombined organic extracts were dried over sodium sulfate
8. concentrationconcentrated
9. customto yield a crude product
10. extractionThe basic heterogeneous solution was extracted 3×300 mL of EtOAc, organic extracts
11. dry with materialdried over sodium sulfate
12. concentrationconcentrated
13. customThe crude product was purified by column chromatography

ORD record

ord-b7e2fe689162471ca7ad244c1acabf30

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07605171B2