ethyl 3-chloro-2,2-dimethylpropanoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 4-[5-(2-Amino-pyrimidin-5-yl)-1-tert-butyl-1H-benzoimidazol-2-yl]-3-[1,2,4]-triazol-1-yl-phenol (300 mg, 0.7 mmol) in DMF (10 mL) is added cesium carbonate (687 mg, 2.1 mmol) followed by Ethyl 3-chloro-2,2-dimethylpropanoate (231 mg, 1.4 mmol) at room temperature. The solution is heated to 90° C. for 72 hours. The solution is cooled to room temperature and is extracted with H2O (10 mL) and EtOAc (3×10 mL). The combined organic layer is dried with Mg2SO4 (500 mg) and is filtered. The filtrate is concentrated and the residue is purified by silica gel flash column chromatography with 10% MeOH in CH2Cl2 as the eluent to afford the title compound (200 mg, 51%). LCMS (ESMS): m/z: 555.40 (M++1). The solution is cooled to room temperature is extracted with H2O (10 mL) and EtOAc (3×10 mL) The combined organic layer is dried with Mg2SO4 (500 mg) is filtered The filtrate is concentrated the residue is purified by silica gel flash column chromatography with 10% MeOH in CH2Cl2 as the eluent

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (2S,4R)-N-(4-Chloro-phenyl)-N-[1-(4-hydroxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide (0.32 g, 0.74 mmol) was dissolved in 10 ml DMF at room temperature and K2CO3 (0.51 g, 3.7 mmol) was added. 3-Chloro-2,2-dimethyl-propionic acid ethyl ester (0.25 g, 1.52 mmol) was added and the reaction was allowed to heat to 90° C. for 6 days. The reaction mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate and water, then extracted three times with ethyl acetate, dried over MgSO4, filtered and concentrated down. The crude residue was purified by silica gel chromatography (60% EtOAc/40% Hexane) to afford the (2S,4R)-3-(4-{4-[acetyl(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-2,2-dimethyl-propionic acid ethyl ester (0.13 g, 32%). The reaction mixture was concentrated in vacuo The residue was partitioned between ethyl acetate and water extracted three times with ethyl acetate dried over MgSO4 filtered concentrated down The crude residue was purified by silica gel chromatography (60% EtOAc/40% Hexane)