| 79.8% |
|
A 1000 ml round-bottomed flask is filled with magnesium (10.7 g, 0.44 mol). Iodine (0.2 g) is sublimated to the magnesium, then diethyl ether (240 ml) is added and under reflux, a solution of 2-fluorobenzyl chloride (47.8 ml, 0.4 mol) and diethyl ether (80 ml) is added to the reaction mixture. The mixture is refluxed for 2 hours and at this temperature a solution of cyclopropanecarboxylic acid dimethylamide (36.2 g, 0.32 mol), prepared according to example 1, and tetrahydrofuran (200 ml) are added. The reaction mixture is stirred for half an hour and under cooling aqueous hydrogen chloride (160 ml, 1:1) is added dropwise to the mixture. The organic layer is dried and the residue is fractionated in vacuo.Boiling point: 61 C / 0.2 HgmmYield: 46.6 g (79.8 %) colourless oilContent (measured by GC): 97.7 %Refractive index: [nD20] = 1.5169 <n="12"/>IR (film): 3010, 1704, 1587, 1494, 1457, 1384, 1234, 1072, 1025.1H-NMR (CDCl3, 500 MHz): 7.25 (dd, IH), 7.20 (t, IH), 7.10 (t, IH), 7.06 (t,IH), 3.87 (s, 2H), 1.99 (m, IH), 1.06 (m, 2H), 0.87 (m, 2H).13C-NMR (CDCl3, 125 MHz): 206.9 (d, J = 1.0 Hz), 161.0 (d, J = 246.1 Hz),131.6 (d, J = 4.4 Hz), 128.8 (d, J= 8.3 Hz), 124.1 (d, J = 3.4 Hz), 121.8 (d, J =16.6 Hz), 115.3 (d, J= 21.5 Hz), 43.5 (d, J= 2.4 Hz), 20.0 (d, J = 1.0 Hz), 11.2. |
| 60.9% |
|
A 1000 ml round-bottomed flask is filled with magnesium (10.7 g, 0.44 mol). Iodine (0.2 g) is sublimated to the magnesium, then ter/-butyl methyl ether (240 ml) is added and under boiling, a solution of 2-fluorobenzyl chloride (47.8 ml, 0.4 mol) and tert-butyl methyl ether (80 ml) is added to the reaction mixture. The mixture is refluxed for 2 hours and at this temperature a solution of cyclopropanecarboxylic acid dimethylamide (36.2 g, 0.32 mol), prepared according to example 1, and tetrahydrofuran (200 ml) are added. The reaction mixture is stirred for half an hour and under cooling aqueous hydrogen chloride (160 ml, 1 :1) is added dropwise to the mixture. The organic layer is dried and the residue is fractionated in vacuo.Yield: 35.6 g (60.9 %) colourless oilContent (measured by GC): 97.7 % Refractive index: [nD20] = 1.5167 |
|
With iodine; magnesium; In tetrahydrofuran; 2-methyltetrahydrofuran; at 40 - 45℃; for 1.5h;Inert atmosphere; |
Into a round-bottomed flask 3.2 g (0.132 mole, 1.50 equiv.) of magnesium and 0.04 g of iodine are added in a slow argon current. To the mixture 60 ml of 2-methyl-tetrahydrofurane and thereafter 14.2 g (0.098 mole, 1.11 equiv.) of 2-fluoro-benzyl-chloride (Formula (2)) are added drop wise. To the Grignard reactant thus obtained a solution of 10 g (0.088 mole, 1.0 equiv.) of cyclopropane-carboxylic acid-dimethylamide (Formula (3)) in 50 ml of tetrahydrofurane is added. The reaction mixture is allowed to stand at 40-45C for an hour and a half whereupon a mixture of 23 ml of concentrated hydrochloric acid and 23 ml of water is added. The two phases are separated; the organic layer is washed with sodium hydrogen carbonate solution and water, washed with water and evaporated. The crude product is analysed with GC. The weight of the crude product is 14.4 g (91.5 %) The ratio of the dibenzyl contamination (Formula (6)) is 1.6 GC area %. |
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