Diethyl 1,1-cyclopropanedicarboxylate

Step 1: Into a 5 L 4 necked round bottomed flask was placed a solution of diethyl malonate (300 g, 1.87 mol) and 1, 2-dibromoethane (634.5 g, 3.38 mol) in DMSO (1.5 L). The mixture was treated with K2C03 (1020 g, 7.39 mol) and Bu4NHSO4 (6.4 g, 19 mmol). The resulting solution was allowed to stir for 48 h at room temperature. The reaction mixture was treated with 2 L of H20 and extracted with 1.5 L of EtOAc (3x). The organic layers were combined, dried over Na2SO4 and concentrated under reduced pressure. The residue was distilled under 5-10 mmHgvacuum at 64-65 °C. This resulted in 400 g (90percent) of diethyl cyclopropane-1, 1-dicarboxylate as an oil.Step 1: Into a 5 L 4 necked round bottomed flask was placed a solution of diethyl malonate (300 g, 1.87 mol) and 1, 2-dibromoethane (634.5 g, 3.38 mol) in DMSO (1.5 L). The mixture was treated with KGeneral procedure: Diethyl malonate 2.53 mL (17 mmol), iodomethane or 1, 2-dibromoethane or 1, 3-dibromoethane(22 mmol), K2CO3 5.7 g (42 mmol) and tetrabutylammonium bromide 0.27 g (0.08 mmol) were addedin DMF. The mixture is stirred for 16 h at room temperature. After evaporation of solvent, the residuewas extracted with ethyl acetate 100 mL three times, and the organic layer was washed with water.After the concentration of the solvent, colorless oil diethyl cyclopropane-1, 1-dicarboxylatederivativeswere obtained (yield 89percent).To a solution of diethyl malonate (3.2 g, 20 mmol) and anhydrous potassium carbonate powder (6.9 g, 50 mmol) in DMF (50.0 mL) was added 1, 2-dibromoethane (4.136 g, 22 mmol). To a solution of diethyl malonate (3.2 g, 20 mmol) and anhydrous potassium carbonate powder (6.9 g, 50 mmol) in DMF (50.0 mL) was added 1, 2- dibromoethane (4.136 g, 22 mmol). After stirring for 2 hrs, catalytic amount of TBAI (0.738 g, 2.0 mmol) was added and the mixture was continued to stir at room temperature for 8 hrs. The reaction mixture was filtered and the solid was washed with diethyl ether 3 times. The filtrate was diluted with water (200 mL) and extracted with diethyl ether (75 mLx4). The combined organic phases were washed with 70 mL of brine, dried over NaTo the equipped with a mechanical stirring device of four in the flask is added malonic acid diethyl ester 40g (249.73mmol), 1, 2 - dichloroethane 32.14g (324.65mmol), sodium iodide 3.75g (24.97mmol), DMF 200 ml and anhydrous potassium carbonate 75.93g (549.41mmol), under the condition of stirring the reaction system heating to reflux, GC monitoring reaction progress, in order to c diethyl malonate disappear as the end point of the reaction. After the reaction, the reaction is cooled down to the room temperature and filtering, cake DMF washing, the filtrate and wash liquid after normal pressure evaporate DMF (can be recycled), to obtain 1, 1 - cyclopropyl acid bis b ester thick 42g (yield of 93percent). The crude without further purification process and can be directly used for the next step reaction.The compound represented by the formula (II), potassium carbonate, and 0.1 mol of tetrabutylammonium bromide, the X is Cl, are mixed in the same manner as in Table 1, and the compound represented by the formula (II) , The reaction bottle is connected with a constant pressure titration funnel, the constant pressure titration funnel is connected with a condenser at its upper end, stirred, heated to reflux, and heated at 120C for 2.5 to 6 hours. The liquid obtained after the reaction is filtered , After washing with ice water in a separatory funnel, the layers are allowed to stand and the lower organic phase is placed in a conical flask and distilled under reduced pressure. The obtained distillate is poured into ice water, extracted with ether, Dried over anhydrous ammonium sulfate, filtered and concentrated to give the compound of formula (I) and the yield was calculated. The results are shown in Table 1.Table 1Diethyl malonate (33.01g), 1, 2-dichloroethane (40.38g), TBAB (2.09g), benzene (100ml), potassium carbonate (72.50g), and Water (l.OOml) were added into 500ml flask and heated to115 DC overnight. The reaction mixture was cooled to room temperature and filtrated. The filtratewas concentrated and followed by purification of flash column to give A31(24.80g ).General procedure: To a 5 mL Schlenk tube were added aryl / heteroaryl acetates 3 (1.0 mmol, 1.0 equiv.), vinyl diphenylsulfonium triflate (434.4 mg, 1.2 mmol, 1.2 equiv.) and DMSO (5 mL). The mixture was stirred at room temperature for 2 min and to the mixture was added DBU (456 mg, 3 mmol, 3.0 equiv.). The mixture was stirred for 12 hours at room temperature till the reaction was complete. To the resulting mixture was added saturated ammonium chloride solution (25 mL), and the mixture was then extracted with EtOAc

Molecular Weight:186.20
XLogP3:1.2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:6
Exact Mass:186.08920892
Monoisotopic Mass:186.08920892
Topological Polar Surface Area:52.6
Heavy Atom Count:13
Complexity:198
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes