3-Cyclopentene-1-carboxylicacid, methy...

To a solution of 1.1 (10 g, 89 mmol) in DCM (100 mL) at 0° C. under NTo a solution of 3-cyclopentene-1-carboxylic acid (Org. Synth. 75, PL95-200, 1998) (31.5 g, 281 mmol) in anhydrous N, N-DIMETHYLFORMAMIDE (300 mL), under an atmosphere of nitrogen, was added potassium carbonate (97 g, 703 mmol), and iodomethane (35 mL, 563 mmol). The resulting mixture was stirred at room temperature for 16 hours, then poured into water (1 litre), and extracted with diethyl ether (3 x 400 mL). The combined diethyl ether layers were washed with water (3 x 500 mL), saturated NACL (200 mL), dried over MGS04, filtered and concentrated I71 VACUO, to give 34 g (96 percent) of crude product. H NMR (CDC13, 500 MHz) : 8 5.64 (s, 2H), 3.68 (s, 3H), 3.11 (quintet, J = 8.5 Hz, 1H), 2.63 (d, J = 8.3 Hz, 4 H).To a solution of 3-CYCLOPENTENE-1-CARBOXYLIC acid (Org. Synth. 75, PL95-200, 1998) (31.5 g, 281 mmol) in anhydrous N, N-DIMETHYLFORMAMIDE (300 mL), under an atmosphere of nitrogen, was added potassium carbonate (97 g, 710 MMOL), and iodomethane (35 mL, 560 mmol). The resulting mixture was stirred at room temperature for 16 h, then poured into water (1 L), and extracted with diethyl ether (3 x 400 mL). The combined diethyl ether layers were washed with water (3 x 500 mL), saturated NACI (200 ML), dried over MGS04, filtered and concentrated in vacuo, to give 34 g (96 percent). 'H NMR (CDCL3, 500 MHz) : 8 5.64 (s, 2H), 3.68 (s, 3H), 3.11 (quintet, J = 8.5 Hz, 1H), 2.63 (d, J = 8.3 Hz, 4 H).INTERMEDIATE 21; Step A; To a solution of 3-cyclopentene-1-carboxylic acid (Org. Synth. 75, p195-200, 1998) (31.5 g, 281 mmol) in anhydrous N, N-dimethylformamide (300 mL), under an atmosphere of nitrogen, was added potassium carbonate (97 g, 710 mmol), and iodomethane (35 mL, 560 mmol). The resulting mixture was stirred at room temperature for 16 h, then poured into water (1 L), and extracted with diethyl ether (3.x.400 mL). The combined diethyl ether layers were washed with water (3.x.500 mL), saturated NaCl (200 mL), dried over MgSOMethod A A well stirred mixture of 9.2 g (0.05 mol) of dimethyl 3-cyclopentene-1, 1-dicarboxylate, 3.6 g (0.06 mol) of sodium chloride, 1.8 ml (0.1 mol) of water and 30 ml of dimethyl sulfoxide was heated, under nitrogen, in an oil bath to 160-165C and kept at this temperature for 18 hours. The progress of the reaction could be conveniently monitored by gas chromatographic analysis. The dark mixture was then cooled to room temperature, poured onto 200 ml of saturated sodium chloride solution and extracted with ether (3 x 100 ml). The combined extracts were washed with saturated aqueous sodium chloride (50 ml), dried over magnesium sulfate and evaporated, leaving 5.1 g (79%) of crude methyl 3-cyclopentene-1-carboxylate. Distillation gave 4.2 g (70%) of pure material, b.p. 147-148C, as a colorless oil.To a solution of 1.1 (10 g, 89 mmol) in DCM (100 mL) at 0 C. under N2 atmosphere was added 1, 1-carbonyldiimidazole (43 g, 267 mmol). The mixture was stirred at room temperature for 4 hours, then MeOH (100 mL) was added. The mixture was allowed to stir overnight. The solvent was evaporated at low temperature to afford 2 (11.2 g, 99%).A stirred solution of cyclopent-3-ene-l-carboxylic acid (250 g, 2.23 mol) in MeOH (2.0 L) at 0 C, was charged with H2S04 (10 mL) dropwise and the reaction mixture was heated at 80 C for 6 h. When TLC analysis showed complete consumption of the starting material, the reaction mixture was concentrated under reduced pressure and the residue was diluted with EtOAc (2.0 L). The organic layer was washed with saturated aqueous NaHC03 (2 L) and brine (2 L). The organic layer was dried over anhydrous Na2S04 and concentrated under reduced pressure to afford title compound (225 g, 80%) as a colorless oil. 1H NMR (400MHz, CDC13): delta 5.67(s, 2H), 3.68 (s, 3H), 3.07-3.15 (m, 1H), 2.61-2.66 (m, 4H).The mixture of methyl cyclopent-3-ene-l -caiboxylate (0.25 mL, 2.0 mmol), i , 4-dichloro-2- iodobenzene (0.27 ml, , 2.0 mmol), palladium acetate (0.2 mmol), DIEA (0.36 mL, 2.0 mmol), water (1 mL) and acetonitrile (5.0 mL) was degassed and flushed with nitrogen. After stirring at 85 C for 3 h, the resulting mixture was cooled and diluted with EtOAc and brine. The organic layer was dried over Na2S04, concentrated under reduced pressure and purified by silica gel column chromatography (15-20% EtOAc/Hex) to afford methyl 3-(2, 5-dichlorophenyl)cyciopent-3-ene-l-carboxylate (432 mg, 80%) as an oil.

Molecular Weight:126.15
XLogP3:1.2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:126.068079557
Monoisotopic Mass:126.068079557
Topological Polar Surface Area:26.3
Heavy Atom Count:9
Complexity:130
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes