Potassium Hydroxide → (-)-7-{[5-(1-Cyclopropyl-2,2,2-trifluoro-1-hydroxyethyl)-1,3-thiazol-2-yl]thio}-4-pyridin-3-yl-2H-chromen-2-one

Temperature

120 °C

Powdered KOH (0.111 g, 1.98 mmol) was added to a solution of (−)-1-cyclopropyl-2,2,2-trifluoro-1-(2-mercapto-1,3-thiazol-5-yl)ethanol (0.507 g, 1.98 mmol) in dry MeOH (2 mL). When a solution was obtained, the reaction mixture was concentrated to dryness. Dry toluene was then added and the mixture was concentrated to dryness again. The residue was dissolved in NMP (2 mL) and 7-bromo-4-pyridin-3-yl-2H-chromen-2-one (0.500 g, 1.65 mmol) was added and the resulting mixture was stirred at 120° C. for 16 h. Once cooled, the mixture was directly applied onto a column of silica gel and chromatographed (acetone/toluene 5:95 to 20:80), affording the title compound. 1H NMR (500 MHz, CDCl3): δ 8.76 (brd, 1H), 8.68 (d, 1H), 7.85 (s, 1H), 7.79 (brd, 1H), 7.50 (m, 2H), 7.31-7.36 (m, 2H), 6.39 (s, 1H), 3.05 (br s, 1H), 1.48 (m, 1H), 0.71 (m, 2H), 0.62 (m, 1H), 0.56 (m, 1H); [α]D=−31.1° (c=1.05, EtOH).

1. customWhen a solution was obtained
2. concentrationthe reaction mixture was concentrated to dryness
3. additionDry toluene was then added
4. concentrationthe mixture was concentrated to dryness again
5. dissolutionThe residue was dissolved in NMP (2 mL)
6. temperatureOnce cooled
7. customchromatographed (acetone/toluene 5:95 to 20:80)

ORD record

ord-97014e6d1ab648928219696b0a34db2f

Source dataset

uspto-grants-2008_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07439260B2