ChemicalBook CAS DataBase List 1-(6-(trifluoroMethyl)pyridin-3-yl)ethanone

1-(6-(trifluoroMethyl)pyridin-3-yl)ethanone synthesis

13synthesis methods

Product Name:1-(6-(trifluoroMethyl)pyridin-3-yl)ethanone
CAS Number:358780-14-0
Molecular formula:C8H6F3NO
Molecular Weight:189.13

To a solution of 2-trifluoromethyl-5-bromopyridine (5.0 g, 22 mmol) in Et2O (50 mL) was added sec-BuLi (0.91 M in cyclohexane, 24 mL, 22 mmol) at -78 °C. After 10 minutes of stirring, N,N-dimethylaminoacetamide (2.3 mL, 24 mmol) dissolved in Et2O (10 mL) was added drop wise. Stirring was continued at -78 °C for 1 h and then at rt over night. The reaction mixture was poured into water (100 mL) and the water phase was extracted with Et2O (3×100 mL). Combined organics were washed with water and brine and dried (MgSO4). After careful evaporation of the solvent, the crude was purified by column chromotography (SiO2, pentane/ether 9/1) to give 1-(6-(Trifluoromethyl)pyridin-3-yl)ethanone (2.3 g, 12 mmol, 54%) as a light yellow solid. 1H NMR (CDCl3) δ 9.26 (br s, 1H) 8.43 (br d, J=5.6 Hz, 1H) 7.83 (br d, J=7.2 Hz, 1H) 2.71 (s, 3H).

1-(6-(Trifluoromethyl)pyridin-3-yl)ethanone synthesis

358780-13-9
95 suppliers
$45.00/100mg

108-59-8 Synthesis

108-59-8
631 suppliers
$5.00/25g

1-(6-(trifluoroMethyl)pyridin-3-yl)ethanone

358780-14-0
126 suppliers
$32.00/100mg

Yield:358780-14-0 79%

Reaction Conditions:

Stage #1:malonic acid dimethyl ester with triethylamine;magnesium chloride in toluene for 2.5 h;light cooling;
Stage #2:6-(trifluoromethyl)nicotinoyl chloride in toluene for 2 h;Cooling;
Stage #3: with hydrogenchloride;watermore than 3 stages;

Steps:

6.i
i) l-(6-Trifluoromethyl-pyridin-3-yl)-ethanone. Magnesium chloride 3.18 g (33.4 mmol) was suspended in 160 ml toluene. After the addition of triethylamine 16.63 ml (119.3 mmol) and malonic acid dimethyl ester 6.58 ml (57.3 mmol) the reaction mixture was stirred for 2.5 hours under light cooling. 6-Trifluoromethyl-nicotinoyl chloride was dissolved in 15 ml toluene and added dropwise under cooling to the reaction mixture. After stirring for 2 hours the mixture was acidified with cone, hydrochloric acid (15 ml). A white precipitate was formed which was dissolved by the addition of water. The water was separated and extracted one time with ethyl acetate and one time with dichloromethane. The combined organic layers were evaporated and the residue was dissolved in 52 ml dimethyl sulfoxide (DMSO) and 2 ml water. The obtained solution was stirred at155 ⁰C for 2.5 hours. After cooling and the addition of 100 ml ice water it was stirred for 15 minutes. The product was isolated by suction and washed with ice water (3 x 15 ml). The solid was dried at 40⁰C to give 7.11 g (79%) of the title compound as white solid. MS: 189.90 (ESI+)¹H-NMR (400 MHz, [D6]DMSO): δ = 2.69 (s, 3H, CH₃), 8.08 (d, IH, 5-H-pyridine), 8.56 (d, IH, 4-H-pyridine), 9.26 (s, IH, 2-H-pyridine)

References:

F. HOFFMANN-LA ROCHE AG WO2008/34579, 2008, A1 Location in patent:Page/Page column 24-25

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