2H-1-Benzopyran-3-ol, 4-[(4-chlorophenyl)thio]-5,8-difluoro-3,4-dihydro- synthesis

Yield:944950-69-0 57%

Reaction Conditions:

with indium(III) chloride in dichloromethane at 20;

Steps:

Step 2: 4-(4-Chloro-phenylsulfanyl)-5, 8-difluoro-chroman-3-ol5,8-Difluoro-2H-chromene oxide 62 (23 g, 0.125 mol) and 4-chloro-benzenethiol (18.1 g, 0.125 mmol) were dissolved in 500 ml_ of dichloromethane and 2.9 g of InCI₃ (0.013 mol) was added. The reaction was stirred at room temperature overnight. The reaction was partitioned between 200 ml_ of dichloromethane and 200 ml_ of water. The organic layer was washed with brine, dried over Na₂SO₄ and concentrated. The product was purified by column chromatography eluting with a gradient from hexanes to 50% EtOAc/hexane over 55 minute to give 23.2 g of alcohol 63 (57%). ¹H NMR, (CDCI₃ 400 MHz δ 7.48 (d, J = 8.8 Hz, 2H), 7.34 (d, J = 8.8 Hz, 2H), 7.01 (m, 1 H), 6.64 (m, 1 H), 4.63 (d, J = 11.7 Hz, 1 H), 4.32-4.41 (m, 2H), 4.12 (m, 1 H).

References:

WO2009/8980,2009,A2 Location in patent:Page/Page column 229-230