| 87% |
With sodium hydride; In tetrahydrofuran; at 0 - 53℃;Inert atmosphere; |
Methyl 2-phenyl-acrylate 1d. In a flask of 250mL provided with magnetic stirrer and N2 atmosphere 4.0g (100mmol, 3 equiv.) of NaH 60% were added to 50mL of n-hexane. The mixture was stirred during 15min, the n-hexane was subtracted and 125mL of THF were then added. The flask was cooled at 0C and then 5g (33.31mmol, 1 equiv.) of methyl phenyl-acetate, 9g (299.9mmol, 9 equiv.) of paraformaldehyde were added. The reaction mixture was heated to 50-53C for around 8min, an intense reflux was initiated and the mixture immediately turns yellow. 50mL of water were added and the solution was extracted with ethyl acetate (20× 3mL). Concentration in a rotatory evaporator gave the crude product, which was purified by flash chromatography (n-hexane/ethyl acetate, 80:20-60:40). Colourless oil, yield 87%. 1H NMR (CDCl3, 400MHz) delta 3.81 (s, 3H), 5.88 (d, J=1.2, 1H), 6.36 (d, J=1.2, 1H), 7.10-7.41 (m, 5H). 13C NMR (CDCl3, 100MHz) delta 52.3, 126.9, 128.2, 128.3, 128.4, 136.8, 141.4, 167.3. HRMS (EI): calcd. for C10H10O2 [M]+: 162.0681, found: C10H10O2: 162.0070. |
| 81% |
|
The compound was synthesized according to a literature method (Ames and Davey J. Chem. Soc. 1958, 1798). To a solution of phenylacetic acid methyl ester (13.58 ml, 100 mmol) in 35 ml of benzene was added diethyl glyoxalate (20.72 ml, 130 mmol). The solution was <n="77"/>allowed to stir at room temperature for 1 hour at which point a solid mass was obtained. Suspending the mass in ether followed by filtration yielded a white powder. The white powder was then suspended in ether and acidified using 5% HCl. The aqueous layer was then removed and the ether layer was washed with saturated NaHCO3, H2O, and brine, dried over MgSO4 and then concentrated under reduced pressure. The resulting yellow oil was charged with 45ml of 37% formaldehyde solution (in water) and 100 ml of water at room temperature. 4Og K2CO3 in 50 ml of water was added via addition funnel to the reaction mixture over a period of 30 minutes. The reaction was then stirred for a further 2 hours at room temperature. The resulting mixture was extracted with ether three times, and the resulting ethereal solution was washed with water, brine, dried over MgSO4, and subjected to Kugelrohr distillation (830C, 0.5 mmHg) to afford the title compound as an oil (81% yield, 14.Ig). 1H NMR (CDCl3, 300MHz) delta:7.50-7.30 (m, 5H), 6.35 (d, J = 1.2 Hz, IH), 5.90 (d, J= 1.2Hz, IH), 4.31 (q, J= 7.2Hz, 2H), 1.36 (t, J= 7.2 Hz, 3H) ppm. |
| 70% |
With tetra-(n-butyl)ammonium iodide; potassium carbonate; In water; N,N-dimethyl-formamide; at 80℃; for 1.5h; |
To a solution of methyl 2-phenylacetate (6) (25.0 g, 170 mmol) in 100 mL of DMF at rt was sequentially added paraformaldehyde (10.0 g, 333 mmol), potassium carbonate (47.4 g, 333 mmol), and tetrabutylammonium iodide (6.27 g, 16.6 mmol). The mixture was then heated to 80 oC with vigorous stirring for 1.5 h then cooled to rt and combined with 200 mL of ethyl acetate. The organic layer was then washed with water, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to give 19.0 g (70%) of the titled compound (7) as a colorless oil which exhibited spectroscopic characteristics identical to the previously reported data for this material:1 1 H NMR (CDCl3): delta 7.38 (m, 5H), 6.35 (d, 1H, J = 0.8 Hz), 5.87 (d, 1H, J = 0.7 Hz), and 3.79 (s, 3H). |
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