2-(2-chlorophenyl)ethanol

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

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

Procedure: To a solution of 5.26 mL (40 mMol) 2-(2-chlorophenyl)ethanol and 8.36 mL (60 mMol) triethylamine in 100 mL tetrahydrofuran were added dropwise 3.25 mL (42 mMol) methanesulfonyl chloride with cooling. The reaction mixture was stirred 4 hours at ambient and was then concentrated under reduced pressure. The residue was partitioned between dichloromethane and water. The organic phase was separated and washed sequentially with water and saturated aqueous sodium chloride. The remaining organics were dried over sodium sulfate and concentrated under reduced pressure to give 9.22 gm (98.3%) of the title compound as a yellow oil. The product was used without further purification. with cooling was then concentrated under reduced pressure The residue was partitioned between dichloromethane and water The organic phase was separated washed sequentially with water and saturated aqueous sodium chloride The remaining organics were dried over sodium sulfate concentrated under reduced pressure

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

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-[4-(benzotriazol-1-yloxy)-6-oxo-6H-pyridazin-1-yl]-3-cyclopentyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide (0.30 g, 0.54 mmol) in acetonitrile (10 mL, 0.055M) was treated with cesium carbonate (0.36 g, 1.10 mmol) and 2-(2-chloro-phenyl)-ethanol (86 μL, 0.65 mmol). The resulting reaction mixture was stirred at 25° C. overnight. The reaction mixture was then heated at 75° C. for 5.5-6 h. At this time, the reaction was partitioned between water and methylene chloride. The organics were dried over sodium sulfate, filtered, rinsed, and concentrated in vacuo. Silica gel column chromatography (AnaLogix 12 g, 50-75% ethyl acetate/hexanes) afforded 2-{4-[2-(2-chloro-phenyl)-ethoxy]-6-oxo-6H-pyridazin-1-yl}-3-cyclopentyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide (114.1 mg, 37%) as a light yellow solid as a mixture of diastereomers. The resulting reaction mixture The reaction mixture was then heated at 75° C. for 5.5-6 h At this time, the reaction was partitioned between water and methylene chloride The organics were dried over sodium sulfate filtered rinsed concentrated in vacuo

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

Procedure: In analogy to the procedure described in example 78.1, 2-(2-chloro-phenyl)-ethanol was reacted with ethyl iodoacetate in the presence of silver trifluoromethanesulfonate and 2,6-di-tert-butylpyridin to give [2-(2-chloro-phenyl)-ethoxy]-acetic acid ethyl ester as yellow liquid. 1H NMR (CDCl3): 1.28 (t, J=7.3 Hz, 3H), 3.09 (t, J=7.1 Hz, 2H), 3.78 (t, J=7.1 Hz, 2H), 4.09 (s, 2H), 4.21 (q, J=7.3 Hz, 2H), 7.13-7.23 (m, 2H), 7.29-7.37 (m, 2H).

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

Procedure: To a solution of 5.26 mL (40 mMol) 2-(2-chlorophenyl)ethanol and 8.36 mL (60 mMol) triethylamine in 100 mL tetrahydrofuran were added dropwise 3.25 mL (42 mMol) methanesulfonyl chloride with cooling. The reaction mixture was stirred 4 hours at ambient and was then concentrated under reduced pressure. The residue was partitioned between dichloromethane and water. The organic phase was separated and washed sequentially with water and saturated aqueous sodium chloride. The remaining organics were dried over sodium sulfate and concentrated under reduced pressure to give 9.22 gm (98.3%) of the title compound as a yellow oil. The product was used without further purification. with cooling was then concentrated under reduced pressure The residue was partitioned between dichloromethane and water The organic phase was separated washed sequentially with water and saturated aqueous sodium chloride The remaining organics were dried over sodium sulfate concentrated under reduced pressure