TRANS-2-(3,4,5-TRIFLUOROPHENYL)CYCLOPENTANOL synthesis

Yield:1263869-56-2 79%

Reaction Conditions:

Stage #1: 3,4,5-trifluoro-1-bromobenzenewith magnesium in tetrahydrofuran;Reflux;
Stage #2: Cyclopentene oxide;copper(l) iodide in tetrahydrofuran at 20; for 2 h;
Stage #3: with water;ammonium chloride in tetrahydrofuran;

Steps:

T.1

To a suspension of magnesium (2.88 g, 118 mmol) in THF (110 mL) was slowly added 5-bromo-l,2,3-trifluorobenzene (25 g, 118 mmol). After the addition, the reaction mixture was heated at reflux for 2 h. To this reaction mixture, copper (I) iodide (1.506 g, 7.91 mmol) and 6-oxabicyclo[3.1.0]hexane (9.93 g, 118 mmol) dissolved in THF (20 mL) were added dropwise. The reaction mixture warmed upon the addition of the epoxide. The reaction was stirred at rt for 2 h at rt. The reaction mixture was quenched by the addition of a solution of ammonium chloride. Ether was added and the organic layer was collected, dried (Na₂SO₄) and concentrated. The crude product was purified by column chromatography on silica gel to give (lS,2R)-2-(3,4,5-trifluorophenyl)cyclopentanol (20.2 g, 93 mmol, 79 % yield).¹H NMR (500 MHz, CDCl₃) δ ppm 6.79 - 7.02 (2H, m), 4.10 - 4.21 (IH, m), 2.75 - 2.91 (IH, m), 2.08 - 2.24 (2H, m), 1.75 - 1.93 (2H, m), 1.50 - 1.75 (2H, m).

References:

WO2011/14535,2011,A1 Location in patent:Page/Page column 134-135