methyl 2,6-dichlorobenzoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: n-Butyl lithium (20.1 mL, 32.2 mmol, 1.6M in hexanes) was added to THF (30 mL) and the solution was cooled to −78° C. Acetonitrile (1.7 mL, 32 mmol) was added dropwise and the reaction stirred at the temperature for 45 minutes. Methyl 2,6-dichlorobenzoate (1.00 g, 4.88 mmol) was dissolved in 2 mL THF and added to the reaction mixture. The reaction stirred at −78° C. for 0.5 hr. The solution was quenched with methanol and warmed to room temperature. The material was diluted with water and 1N HCl. The solution was then extracted with Ethyl acetate, dried, and concentrated to give 1.08 g of desired product at 85% purity. Material used as is in the next step. added to the reaction mixture The reaction stirred at −78° C. for 0.5 hr The solution was quenched with methanol warmed to room temperature The material was diluted with water and 1N HCl The solution was then extracted with Ethyl acetate dried concentrated

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: n-Butyl lithium (20.1 mL, 32.2 mmol, 1.6M in hexanes) was added to THF (30 mL) and the solution was cooled to −78° C. Acetonitrile (1.7 mL, 32 mmol) was added dropwise and the reaction stirred at the temperature for 45 minutes. Methyl 2,6-dichlorobenzoate (1.00 g, 4.88 mmol) was dissolved in 2 mL THF and added to the reaction mixture. The reaction stirred at −78° C. for 0.5 hr. The solution was quenched with methanol and warmed to room temperature. The material was diluted with water and 1N HCl. The solution was then extracted with Ethyl acetate, dried, and concentrated to give 1.08 g of desired product at 85% purity. Material used as is in the next step. added to the reaction mixture The reaction stirred at −78° C. for 0.5 hr The solution was quenched with methanol warmed to room temperature The material was diluted with water and 1N HCl The solution was then extracted with Ethyl acetate dried concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,6-Dichlorobenzoic acid (5.00 g, 26.2 mmol) was diluted in dimethylcarbonate (44 mL, 530 mmol). 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) (3.91 mL, 26.2 mmol) was added last. The reacted was refluxed for 2 days. Upon cooling, the solution was diluted with ethyl acetate and water. The aqueous layer was removed and the organic layer was washed with water, 2N HCl (2×'s), sat. NaHCO3 (2×'s), and twice with water. The organic layer was dried over sodium sulfate, filtered, and concentrated to yield 4.61 g (86%) of the desired compound as a clear oil. The reacted was refluxed for 2 days Upon cooling The aqueous layer was removed the organic layer was washed with water, 2N HCl (2×'s), sat. NaHCO3 (2×'s), and twice with water The organic layer was dried over sodium sulfate filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of diisopropylamine (22 ml) in dry tetrahydrofuran (160 ml) cooled to 0° C. under an inert atmosphere was added n-butyl lithium (2.5M, 67 ml) dropwise. The solution was stirred for 30 minutes at 0° C., then added to a solution of methyl 2,6-dichlorobenzoate (26.62 g) in dry tetrahydrofuran (160 ml) cooled to -78° C. under an inert atmosphere. After 1.5 hours at this temperature the mixture was poured onto excess solid carbon dioxide and left to stand overnight. The solvent was evaporated in vacuo and the residue acidified with 2N hydrochloric acid. This was then extracted with ethyl acetate, dried over anhydrous magnesium sulphate and evaporated in vacuo to yield 2,4-dichloro-3-methoxycarbonylbenzoic acid (32.37 g) as a solid, NMR (DMSO D6) δ3.93 (3H,s), 7.70 (1H, d), 7.91 (1H,d). cooled to -78° C. under an inert atmosphere left to stand overnight The solvent was evaporated in vacuo This was then extracted with ethyl acetate dried over anhydrous magnesium sulphate evaporated in vacuo

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: n-Butyl lithium (20.1 mL, 32.2 mmol, 1.6M in hexanes) was added to THF (30 mL) and the solution was cooled to −78° C. Acetonitrile (1.7 mL, 32 mmol) was added dropwise and the reaction stirred at the temperature for 45 minutes. Methyl 2,6-dichlorobenzoate (1.00 g, 4.88 mmol) was dissolved in 2 mL THF and added to the reaction mixture. The reaction stirred at −78° C. for 0.5 hr. The solution was quenched with methanol and warmed to room temperature. The material was diluted with water and 1N HCl. The solution was then extracted with Ethyl acetate, dried, and concentrated to give 1.08 g of desired product at 85% purity. Material used as is in the next step. added to the reaction mixture The reaction stirred at −78° C. for 0.5 hr The solution was quenched with methanol warmed to room temperature The material was diluted with water and 1N HCl The solution was then extracted with Ethyl acetate dried concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,6-Dichlorobenzoic acid (5.00 g, 26.2 mmol) was diluted in dimethylcarbonate (44 mL, 530 mmol). 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) (3.91 mL, 26.2 mmol) was added last. The reacted was refluxed for 2 days. Upon cooling, the solution was diluted with ethyl acetate and water. The aqueous layer was removed and the organic layer was washed with water, 2N HCl (2×'s), sat. NaHCO3 (2×'s), and twice with water. The organic layer was dried over sodium sulfate, filtered, and concentrated to yield 4.61 g (86%) of the desired compound as a clear oil. The reacted was refluxed for 2 days Upon cooling The aqueous layer was removed the organic layer was washed with water, 2N HCl (2×'s), sat. NaHCO3 (2×'s), and twice with water The organic layer was dried over sodium sulfate filtered concentrated