1,4-Diethyl 2-(2-oxopropyl)butanedioate

Under mechanical stirring, 194 g of A mixture of 5.4 g (23 mmol) of A 1.0 g. portion of Aliquat 336 (tricaprylyl methyl ammonium chloride), 35.0 ml. of toluene, 9.51 ml. (75 mmole) of ethyl acetoacetate, 9.48 ml. (75 mmole) of ethyl chloropropionate, 1.0 g. (<60 mesh) of potassium iodide, and 100 milliequivalents, 13.8 g. of less than 80 mesh, oven-dried potassium carbonate are placed in a 250 ml. 3-necked flask equipped with a condenser, mechanical stirrer and thermometer. The mixture is stirred at 75-80 C. for about 6 hours to ensure formation of diethyl alpha-acetyl-alpha'-methylsuccinate, without substantial decomposition by further heating.(1) 2404.5 g of toluene was sequentially added to a 3 L reaction flask.Anhydrous ethanol 96.75g (2.1mol) and solid sodium ethoxide 285.8g (4.2mol), Stirring to 38 C, when the above solids are completely dissolved, To the resulting mixture, 801.5 g (3.5 mol) of the compound of the formula (2) was added dropwise for 3 hours.After the completion of the dropwise addition, the reaction was continued for 2 hours to obtain an ECOC reaction mixture; (2) The ECOC reaction mixture obtained in the step (1) was cooled to 25 C, and 106.2 g (1.05 mol) of triethylamine was added.After the triethylamine was completely dissolved, 439.03 g (4.2 mol) of cyclopropanoyl chloride was added dropwise thereto for 2.5 hours.After the completion of the dropwise addition, the reaction was continued for 1 hour, and then 2, 405 g of tap water was added, washed with water, allowed to stand, and layered.The aqueous layer was separated, and the toluene layer was concentrated under a vacuum (-0.095 MPa) to remove about 1300 g of toluene to obtain an ECCOC reaction mixture; (3) 102.5 g (0.45 mol) of benzyltriethylammonium chloride was sequentially added to the ECCOC reaction mixture obtained in the step (2) at 23 C.63.8 g (0.75 mol) of acetone cyanohydrin and 455 g (4.5 mol) of triethylamine were stirred and heated to 60 C, and the reaction was kept for 3 hours.Then, the temperature was lowered to 7 C, 1603 g of tap water was added, stirred, and the layer was allowed to stand. The toluene layer was further added with tap water 200 g, stirred, and the toluene layer was separated and the toluene layer was removed from the solvent to separate the water layer.3007.5 g of petroleum ether was added to the combined aqueous layer, and the temperature was lowered to 18 C, and 30% by weight of hydrochloric acid was added dropwise.Until the pH of the water layer is 2, the layer is allowed to stand, and the obtained aqueous layer is further added with 1000 g of petroleum ether for extraction once.The mixture was allowed to stand for stratification, and the petroleum ether layer was combined, and the combined petroleum layers were slowly cooled to 0 C for 4 hours. The solid was precipitated and filtered to give a 4-cyclopropyl(hydroxy)methylene-3, 5-dionecyclohexanecarboxylic acid ethyl ester.The mother liquor obtained after filtration is removed from the solvent for use, and the obtained residue is recorded as mother liquor A4.The obtained wet base is heated and desolvated in the reaction flask to remove the solvent.592 g of a yellow-brown liquid was obtained as ethyl 4-cyclopropyl(hydroxy)methylene-3, 5-dionecyclohexanecarboxylate, the purity was 97%, and the yield was 65% by weight.To the reaction flask was added 410 g of tert-butyl 4-oxopentane-1, 2-dicarboxylate-3-carboxylate, 1000 mL of toluene and 21.6 gP-toluenesulfonic acid, stirred for 2h. After washing with 200 mL of water and 200 mL of 5% sodium bicarbonate solution successively, the solution was removed under reduced pressure 256 g of Step 2 Add to the reaction flask2 - [(acetyl) (tert-butoxycarbonyl)] methyl-1, 4-butanedioate 408 g, Toluene 1000mL, p-toluenesulfonic acid 21.6g, the reaction 2h. Then use 200mL of waterAnd 200mL5% sodium bicarbonate solution After washing, Dehydration vacuum derivedDiethyl 2-acetylmethyl-1, 4-butanedioate256g.