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CAS No. : | 137052-08-5 | MDL No. : | MFCD08704647 |
Formula : | C7H12O2 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | VNMXIOWPBADSIC-UHFFFAOYSA-N |
M.W : | 128.17 | Pubchem ID : | 9877365 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-H335 | Packing Group: | |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Add 2 M isopropylmagnesium chloride in tetrahydrofuran (520.22 mL, 3.0 eq) to a mixture of methyl tetrahydro-2H-pyran-4-carboxylate (46.30 mL, 346.81 mmol) and Nu,Omicron-dimethylhydroxylamine hydrochloride (52.44 g, 1.6 eq) in tetrahydrofuran (2.43 L) during 15 minutes at -20C under nitrogen. After 30 min, add saturated aqueous ammonium chloride (400 mL) to the reaction at -20C. Extract the aqueous solution with methyl tert-butyl ether (250 mL x 3). Wash the combined organics with saturated aqueous sodium chloride. Dry over anhydrous magnesium sulfate and concentrate in vacuo. Add dichloromethane (500 mL), filter through Celite and concentrate in vacuo. Add tetrahydrofuran (700 mL), then add 3 M methyl magnesium chloride intetrahydrofuran (231.21 mL, 2.0 eq) dropwise over 15 minutes at 7C. After 40 minutes, add saturated aqueous ammonium chloride (250 mL) to the reaction. Extract the aqueous solution with methyl tert-butyl ether (250 mL x 2). Dry over anhydrous magnesium sulfate and concentrate in vacuo. Purify by silica gel chromatography, eluting with 2: 1 hexanes: ethyl acetate to 1 : 1 hexanes: ethyl acetate, to give 1 -(tetrahydro-pyran-4-yl)- ethanone (33.18 g, 75%). 'H NMR (300 MHz, DMSO-d6) delta 3.98 (m, 2H), 3.42 (m, 2H), 2.52 (m, 1H), 2.15 (s, 3H), 1.74 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | In tetrahydrofuran; diethyl ether; at -60 - 0℃; for 6h; | [0240] A flask was charged with <strong>[156353-01-4]N-methoxy-N-methyltetrahydro-2H-pyran-4-carboxamide</strong> 2 (11.7 g, 67.5 mmol) andTHF (350 mL). The resulting mixture was immersed in a cooling bath at -60C, 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, 0% to 100% EtOAc/hexanes) to give 4-acetyltetrahydro-4H-pyran 3 (7.05 g, 55.0 mmol, 81%). 1HNMR (400 MHz, CDCl3) for 3: delta 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). |
In tetrahydrofuran; diethyl ether; at 0℃; | Add 3 M methyl magnesium bromide in diethyl ether (1.14 L, 2.0 eq) to a solution of <strong>[156353-01-4]N-methoxy-N-methyl-tetrahydropyran-4-carboxamide</strong> (296 g, 1.71 mol) intetrahydrofuran (2.96 L) over one hour at 0C. Stir for an additional two hours, then pour the contents into a mixture of ice/water. Extract with methyl tert-butyl ether. Dry the organics over anhydrous magnesium sulfate and concentrate in vacuo to give 1-(tetrahydro-pyran-4-yl)-ethanone (105 g, 48%). ? NMR (300 MHz, DMSO-d6) delta 3.98 (m, 2H), 3.42 (m, 2H), 2.52 (m, 1H), 2.15 (s, 3H), 1.74 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With methylmagnesium bromide; In tetrahydrofuran; ethyl acetate; | Step 2 A flask was charged with <strong>[156353-01-4]N-methoxy-N-methyltetrahydro-2H-pyran-4-carboxamide</strong> 2 (11.7 g, 67.5 mmol) and THF (350 mL). The resulting mixture was immersed in a cooling bath at -60 C., and methylmagnesium bromide (3.0 M in ether, 33.8 mL, 101.4 mmol) was added via syringe over ~8 min. The temperature of the bath was allowed to rise to 0 C. over 6 h. At that time, the reaction was diluted with water and EtOAc and stirred vigorously for 10 min. The phases were separated, and the aqueous layer was extracted with EtOAc. The organic portions were combined, washed with brine, dried over MgSO4, filtered, and concentrated. The crude residue was subjected to column chromatography (120 g silica, 80 mL/min, 0% to 100% EtOAc/hexanes) to give 4-acetyltetrahydro-4H-pyran 3 (7.05 g, 55.0 mmol, 81%). 1H NMR (400 MHz, CDCl3) for 3: delta 3.95 (ddd, J=11.6, 4.4, 2.8 Hz, 2H), 3.38 (dt, Jd=2.8 Hz, Jt=11.6 Hz, 2H), 2.50 (m, 1H), 2.12 (s, 3H), 1.75 (m, 2H), 1.65 (m, 2H). LCMS for 3 (conditions D): tR=0.83 min, m/e=129.4 (M+H, base). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74.28% | With bromine; In methanol; at -10 - 10℃; for 1.5h; | Method 2: (0049) Cool a solution of 1-tetrahydropyran-4-ylethanone (10 g, 78.02 mmol) in methanol (MeOH; 50 mL) to -10 C. Add bromine (4.01 mL, 78.02 mmol) dropwise. Stir the mixture at 0 C. for 45 minutes and then at 10 C. for 45 minutes. Add an aqueous solution of sulfuric acid (11M, 27.5 mL, 302.50 mmol) and stir the resulting mixture at room temperature overnight. Add water and extract with diethyl ether three times. Combine the organic layers. Wash with an aqueous solution of sodium bicarbonate and water. Dry over anhydrous sodium sulfate and concentrate under reduced pressure to give the title compound (12 g; 74.28% yield) as a white solid. 1H NMR (400.13 MHz, CDCl3) delta 4.00 (m, 2H), 3.95 (s, 2H), 3.45 (m, 2H), 2.98 (m, 1H), 1.78 (m, 4H). |
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