1-(6-Methyl-2-pyridinyl)ethanone

2-Acetyl-6-methylpyridine is an aromatic ketone.

To a -75°C solution of oxalyl chloride (20 mL, 225 mmol, 1.1 equiv) in methylene chloride (300 mL) was slowly added a solution of dimethylsulfoxide (32 mL, 2.2 equiv) in methylene chloride (400 mL) over 1 hour. The resulting solution was stirred at-75°C for 10 min, and then slowly treated with a solution of [1- (6-] methyl-pyridin-2-yl) -ethanol (28 [G, ] 204 mmol, 1 equiv) in methylene chloride (600 mL). The reaction mixture was stirred for 10 min at the same temperature, and then slowly treated with triethylamine (140 mL, 1. [02 MOL, 5APOS;EQUIV).] The resulting, mixture was warmed to [20° OVER] 2 hours, and then quenched with water (500 mL). The organic phase was separated, dried over magnesium sulfate and concentrated in vacuo to yield the crude material. Silica gel chromatography (3: 1 hexanes/ethyl acetate) yielded [1- (6-METHYL-PYRIDIN-2-YL)-ETHANONE] (25.36 g, 92percent).Step B General procedure: Manganese dioxide (1.04 g) was added to a solution of (2-methoxypyridin-4-yl)methanol (417 mg) in ethyl acetate (5 mL), followed by refluxing for 1.5 hours. Manganese dioxide (1.04 g) was added thereto, followed by refluxing for 1.5 hours. The reaction mixture was cooled to room temperature, the insoluble materials were filtered off, and the solvent was distilled off under reduced pressure. The obtained residues were purified by silica gel column chromatography (hexane:ethyl acetate=9:1'4:6), whereby 2-methoxyisonicotinic aldehyde (260 mg) was obtained as a colorless oily materialTo a stirred solution of l-(6- methylpyridin-2-yl)ethan-l-one (1.40 g, 10.36 mmol) in DCM (14 mL) was added DAST (3.34 g, 20.72 mmol) dropwise at 5 C. The reaction mixture was warmed to room temperature and stirred at this temperature for 4 days. The reaction mixture was quenched by the addition of sat. NaHCCT (20 mL) at 5 C. The resulting mixture was extracted with CH2CI2 (3 x 20 mL). The combined organic extracts were washed with brine (30 mL), dried over anhydrous Na2S04, filtered and concentrated. The residue was purified on silica gel column with PE/EtOAc (0-10%) to afford 2-(1, 1-difluoroethyl)-6-methylpyridine (448 mg, 27.5%) as a colorless oil.[00261] Step 2: 1-(6-methylpyridin-2-yl) ethan-l-one. To a stirred solution of N-methoxy- N, 6-dimethylpyridine-2-carboxamide (1.8 g, 9.99 mmol) in THF (20 mL) was added MeMgBr (6.7 mL, 3M in THF, 20.1 mmol) dropwise at -30 C under nitrogen atmosphere. The mixture was allowed to warm to room temperature slowly, then stirred for 2 h at room temperature. The reaction was quenched with 2 mL of aqueous NH4Cl at room temperature. The resulting mixture was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na2S04. After filtration, the filtrate was concentrated. The residue was purified on silica gel column with PE/EA (0-30%) to afford l-(6-methylpyridin-2- yl) ethan-l-one (1.4 g, 100%) as a yellow oil. ES-MS (m/z) [M+l]+ = 136.0.

Molecular Weight:135.16
XLogP3:1.3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:135.068413911
Monoisotopic Mass:135.068413911
Topological Polar Surface Area:30
Heavy Atom Count:10
Complexity:133
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes