Sodium Hydroxide → (2-(5,5-Dimethyl-1-cyclopenten-1-yl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methanol

Participants

Reaction Conditions

Reaction Steps

A mixture of compound T2.5 (1.80 g, 5.80 mmol), 2-(5,5-dimethylcyclopent-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (T2.2)(1.40 g, 6.4 mmol), S-Phos (0.48 g, 1.20 mmol), tripotassium phosphate (3.10 g, 15.0 mmol) and palladium acetate (0.13 g, 0.58 mmol) in DMF (10.0 mL) and water (1.0 mL), was purged with N2 three times. The resulting mixture was heated at 100° C. overnight. EtOAc (120 mL) was added, and the mixture was washed with brine (25×2 mL). The organic layer was dried with MgSO4. The residue was purified by CombiFlash® silica gel column chromatography, eluting with hexane/EtOAc, 9/1 to give the Suzuki coupling product as an intermediate, ethyl 2-(5,5-dimethyl-1-cyclopenten-1-yl)-2′-fluoro-5′-(methyloxy)-1,1′-biphenyl-4-carboxylate. MS ESI (pos.) m/e: 369.1 (M+H)+. To a solution of ethyl 2-(5,5-dimethyl-1-cyclopenten-1-yl)-2′-fluoro-5′-(methyloxy)-1,1′-biphenyl-4-carboxylate (1.00 g, 3.0 mmol) in THF (10.0 mL), was slowly added LAH, (1.0M solution in diethyl ether, 4.0 mL, 4.0 mmol) at 0° C. After the addition, the reaction mixture was stirred at 40° C. for 1.5 hours, and then at room temperature for 2 hours. A mixture of water (0.22 mL) in THF (2.0 mL) was slowly added and then 15% sodium hydroxide (0.22 mL) was added at 0° C. Finally, water (0.65 mL) was added at room temperature. The solid was removed by filtration, and the solvent was removed under reduced pressure. The residue was purified by CombiFlash® silica gel column chromatography, eluting with hexane/EtOAc, 90/10 to 70/30) to give the title compound T2.6. 1H NMR (400 MHz, CDCl3) δ ppm. 7.24 (s, 2H), 7.09-7.21 (m, 1H), 6.84-6.96 (m, 1H), 6.68-6.72 (m, 2H), 5.43 (s, 1H), 4.65 (s, 2H), 3.66 (s, 3H), 2.17 (td, 2H), 1.77 (b, 1H), 1.58 (t, 2H), 0.78 (s, 6H). MS ESI (pos.) m/e: 309.1 (M−HO)+, 345.2 (M+H3O)+.

Provenance & Evidence