1,3-difluoropropan-2-ol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from rac-[1-(4-chloro-phenyl)-2-(4-hydroxy-phenyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester and 1,3-difluoro-2-propanol in analogy to Example 9c): MS (ISN): 438.1 (M−H)−.

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was synthesized as described for Intermediate example I-81 in 47% yield starting from ethyl 6-chloronicotinate and 1,3-difluoro-2-propanol. The reduction was performed using 3 equiv of lithium hydroxide, the reaction mixture was stirred at ambient temperature over night; 1H NMR (400 MHz, DMSO-d6) δ ppm 8.71 (d, 1 H), 8.19 (dd, 1 H), 6.99 (d, 1 H), 5.62-5.80 (m, 1 H), 4.77-4.87 (m, 2 H), 4.65-4.75 (m, 2 H); MS (ESI) m/z 216[M−H+].

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was synthesized as described for Intermediate example I-81 in 47% yield starting from ethyl 6-chloronicotinate and 1,3-difluoro-2-propanol. The reduction was performed using 3 equiv of lithium hydroxide, the reaction mixture was stirred at ambient temperature over night; 1H NMR (400 MHz, DMSO-d6) δ ppm 8.71 (d, 1 H), 8.19 (dd, 1 H), 6.99 (d, 1 H), 5.62-5.80 (m, 1 H), 4.77-4.87 (m, 2 H), 4.65-4.75 (m, 2 H); MS (ESI) m/z 216[M−H+].

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Di-tert-butyl azodicarboxylate (719 mg, 3.12 mmol) was added in one portion to pyridin-4-ol (YY) (297 mg, 3.12 mmol), 1,3-difluoropropan-2-ol (100 mg, 1.04 mmol) and Polymer supported triphenylphosphine (1.89 mmol/g; 1016 mg, 3.12 mmol) in dichloromethane (10 mL) at 20° C. under air. The resulting suspension was stirred at 20° C. for 4 hours. The mixture was filtered and the solvent evaporated to a yellow oil. The reaction mixture was diluted with dichloromethane (25 mL), and washed sequentially with 2M NaOH (2×10 mL) and saturated brine (10 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. This was re-dissolved in dichloromethane (25 mL), and washed with 2M HCl (10 mL). The aqueous layer was basified with 2M NaOH and extracted with dichloromethane (×3). The combined organic layers were dried over MgSO4, filtered and evaporated to afford the desired compound as a viscous oil (90 mg, 50%); 1H NMR (400.132 MHz, CDCl3) δ 4.60-4.67 (2H, m), 4.71-4.76 (2H, m), 4.78-4.90 (1H, m), 6.92 (2H, d), 8.48 (2H, d); m/z (LC-MS, ESI+), RT=1.53 (M+H 174). at 20° C. The mixture was filtered the solvent evaporated to a yellow oil The reaction mixture was diluted with dichloromethane (25 mL) washed sequentially with 2M NaOH (2×10 mL) and saturated brine (10 mL) The organic layer was dried over MgSO4 filtered evaporated to afford crude product washed with 2M HCl (10 mL) extracted with dichloromethane (×3) The combined organic layers were dried over MgSO4 filtered evaporated