7H-Oxireno[c][1]benzopyran, 2,5-difluoro-1a,7a-dihydro- synthesis

Yield:944950-67-8 60%

Reaction Conditions:

with 3-chloro-benzenecarboperoxoic acid in dichloromethane at 20; for 0.5 h;

Steps:

Scheme 15:Step 1 : 5,8-Difluoro-2H-chromene oxide5,8-Difluoro-2H-chromene 61 (35g, 0.21 mol) was dissolved in 500 ml_ of dichloromethane and 93 g of MCPBA (77%, 0.42 mol) was added. The reaction was stirred at room temperature for 30 minutes. The reaction was quenched with a solution of 50 g Na₂S₂O₃ in 500 ml_ water. The organic layer was washed with two 500-mL portions of 2N NaOH solution, 200 ml_ of brine, dried over Na₂SO₄ and concentrated. The residue was recrystalized from EtOAc/Hexane solution to give rise to 21.6 g pure product 62. The residue from mother liquor was purified by column chromatography eluting with a gradient from hexanes to 25% EtOAc/hexanes over 55 minute to obtain an additional 1.4 g of 62. Total Yield: 23 g, 60%. ¹H NMR (CDCI₃ 400 MHz δ 7.00 (m, 1 H), 6.63 (m, 1 H), 4.67 (d, J = 12.4 Hz, 1 H), 4.27 (m, 2H), 3.84 (d, J = 4.4Hz, 1 H).

References:

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