1-(Tetrahydro-2H-pyran-4-yl)ethanone

In a flask made of glass having an inner volume of 10 ml and equipped with a stirring device, a thermometer, a dropping funnel and a reflux condenser were charged 202 g (1.0 mol) of 4-acetyl-4-methoxycarbonyltetrahydropyran with a purity of 95percent and synthesized in the same manner as in Reference and 720 ml of methanol, and the temperature of the mixture was raised to 35°C with stirring. Then, to the mixture was gently added dropwise a mixed solution comprising 201 g (2.0 mol) of 35percent by weight aqueous hydrogen peroxide solution and 91 ml (0.73 mol) of 8 mol/l aqueous sodium hydroxide solution, and the mixture was reacted at 40°C for 5 hours with stirring. After completion of the reaction, to the resulting reaction mixture was added a saturated aqueous sodium sulfate solution to decompose the remaining hydrogen peroxide, then, the mixture was concentrated under reduced pressure, and the concentrate was extracted three times with 500 ml of ethyl acetate. The organic layer was distilled under reduced pressure (90 to 92°C, 2.0 kPa) to give 113 g (Isolation yield: 85percent) of 4-acetyltetrahydropyran with a purity of 99percent (areal percentage by gas chromatography) as a colorless liquid. Physical properties of the 4-acetyltetrahydropyran are as follows. CI-MS (m/e); 129 (M+1) Example 3 The mixture of methyl acetylacetate (24.770 g, 211.18 mmol), bis(2-chloroethyl) ether (30.506 g, 211.18 mmol), potassium carbonate (64.861 g, 464.59 mmol) and sodium iodide (31.974 g, 211.18 mmol) in N, N-dimethylformamide (1065 ml) was heated at 80°C for 18 hours. The mixture was cooled to room temperature, further portions of potassium carbonate (29.430 g, 210.80 mmol) and sodium iodide (31.974 g, 211.18 mmol) were added and the whole was heated at 80°C for further 2 hours. The reaction mixture was filtered over celite, washed with ethyl acetate (500 ml), then organic layer was washed with water (300 ml), brine (150 ml) and dried over sodium sulphate. Drying agent and solvent were removed to obtain 26.600 g of the intermediate compound methyl 4-acetyl- tetrahydro-2H-pyran-4-carboxylate. To the obtained compound (26.600 g, 112.47 mmol) isopropanol (125 ml), water (125 ml) and concentrated sulphuric acid (55.151 g, 562.37 mmol) were added and the whole was heated at reflux for 48 hours. The mixture was alkalized with sodium hydroxide solution (45.5 g NaOH in 500 ml of water). Aqueous layer was extracted with chloroform (3 x 100 ml). Extracts were dried over sodium sulphate. Crude product obtained after removing drying agent and solvent in the form of a brown liquid was distilled under reduced pressure using Vigreux column and collecting fraction boiling at 75-83°C/20 mm Hg. 10.874 g of the title product were obtained (yield 36.4percent) in the form of a colorless liquid.[0240] A flask was charged with N-methoxy-N-methyltetrahydro-2H-pyran-4-carboxamide 2 (11.7 g, 67.5 mmol) andTHF (350 mL). The resulting mixture was immersed in a cooling bath at -60°C, and methylmagnesium bromide (3.0 Min ether, 33.8 mL, 101.4 mmol) was added via syringe over ∼ 8 min. The temperature of the bath was allowed to rise to0 °C over 6h. At that time, the reaction was diluted with water and EtOAc and stirred vigorously for 10 min. The phaseswere separated, and the aqueous layer was extracted with EtOAc. The organic portions were combined, washed withbrine, dried over MgSO4, filtered, and concentrated. The crude residue was subjected to column chromatography (120g silica, 80 mL/min, 0percent to 100percent EtOAc/hexanes) to give 4-acetyltetrahydro-4H-pyran 3 (7.05 g, 55.0 mmol, 81percent). 1HNMR (400 MHz, CDCl3) for 3: δ 3.95 (ddd, J = 11.6, 4.4, 2.8 Hz, 2 H), 3.38 (dt, Jd = 2.8 Hz, Jt = 11.6 Hz, 2 H), 2.50 (m, 1 H), 2.12 (s, 3 H), 1.75 (m, 2 H), 1.65 (m, 2 H). LCMS for 3 (conditions D): tR = 0.83 min, m/e = 129.4 (M+H, base).

Molecular Weight:128.17
XLogP3:0.3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:128.083729621
Monoisotopic Mass:128.083729621
Topological Polar Surface Area:26.3
Heavy Atom Count:9
Complexity:104
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes