(2'-TRIFLUOROMETHYLBIPHENYL-4-YL)-METHANOL synthesis

Yield:-

Reaction Conditions:

with sodium tetrahydroborate in methanol at 20; for 1 h;

Steps:

39.B

To a solution of the product of Example 36, Step A (0.15 g, 0.6 mmol) in MeOH (3 m) NaBH₄ (0.028 g; 0.74 mmol) was added in portion wise at room temperature. After 1 h of stirring the solvent was evaporated and the residue was diluted to 20 ml with EtOAc and washed with H₂O. The organic layer was separated, dried over MgSO₄ and filtered. The filtrate was evaporated to dryness and the residue (0.25 g, 0.99 mmol) was dissolved in anhydrous THF (5 ml). To this DIPEA (0.19 ml, 1 .1 mmol) was added at 0 ⁵C under N₂, with stirring, followed by SOCI₂ (0.08 ml, 1 .1 mmol). This was stirred overnight at room temperature. The solvent was distilled off and the crude product was diluted to 20 ml with EtOAc and washed with NaHCO₃ solution. The organic layer was separated, dried over MgSO₄ and filtered. The filtrate was passed through silica gel bead and washed with fresh EtOAc (20 ml). The combined filtrates were evaporated to dryness to give the title compound (0.24 g, 89%) as colourless oil. ¹ H-NMR (CDCI₃) 4.64 (s, 2H); 7.30 (d, 3H, J = 8.12 Hz); 7.4 - 7.58 (m, 4H); 7.73 (d, 2H, J = 7.84 Hz).

References:

WO2010/42998,2010,A1 Location in patent:Page/Page column 100