1-(4-CHLORO-PHENYL)-2-PYRIDIN-4-YL-ETHANONE synthesis

7synthesis methods

Product Name:1-(4-CHLORO-PHENYL)-2-PYRIDIN-4-YL-ETHANONE
CAS Number:58158-45-5
Molecular formula:C13H10ClNO
Molecular Weight:231.68

108-89-4
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623-03-0 Synthesis

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1-(4-CHLORO-PHENYL)-2-PYRIDIN-4-YL-ETHANONE

58158-45-5
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Yield:58158-45-5 52%

Reaction Conditions:

Stage #1: picolinewith lithium diisopropyl amide in tetrahydrofuran at -78 - 0; for 1 h;
Stage #2: 4-Cyanochlorobenzene in tetrahydrofuran at -78 - 20;
Stage #3: with sodium hydroxide;water;hydrogen bromidemore than 3 stages;

Steps:

3.3A

Example 3; 7-(4-Chlorophenyl)-6-(pyridin-4-yl)-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyrimidin-3(2H)-one; 3A: 1-(4-Chlorophenyl)-2-(pyridin-4-yl)ethanone; To a cooled (-78° C.) solution of LDA (2.0 molar solution in THF, 27 mL, 54 mmol) was slowly added a solution of 4-methyl pyridine (5.0 gm, 53.7 mmol) in THF (50 mL) over a period of 30 min under argon. The resulted deep red solution was stirred at 0° C. for 30 min. The reaction mixture was cooled to -78° C. and a solution of 4-chlorobenzonitrile (8.3 gm, 60.3 mmol) in THF (50 mL) was added over a 40 min period. The reaction mixture was stirred at -78° C. for 2 h and then at room temperature overnight. The reaction mixture was diluted with water (100 mL) and acidified to pH 3-4 with 48% HBr. The volatile solvents were evaporated from the reaction mixture and the residual aqueous solution was stirred at reflux for 1 h. The reaction mixture was cooled to room temperatue and extracted with ether (2×30 mL). The aqueous layer was neutralized with 1.0 N NaOH followed by extraction with EtOAc (3×50 mL). The combined organic extracts were washed with saturated aqueous sodium chloride (2×25 ml), dried over MgSO₄and concentrated to obtain a crude product. This material was purified on a silica gel column (40% EtOAc/hexanes) to obtain 3A (6.5 g, 52%) as yellow solid. HPLC RT: 1.27 min; M+H=232.

References:

US2006/287342,2006,A1 Location in patent:Page/Page column 12