2-氯-4-溴苯乙酸甲酯

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (4-Bromo-2-chloro-phenyl)-acetonitrile (1.98 g, 8.6 mmoles) was dissolved into MeOH (50 mL) and water (5 mL), and the resulting homogeneous mixture was chilled to 0° C. To this stirring (cold) mixture was slowly (carefully) added concentrated HCl (25 mL). After the addition was complete the mixture was refluxed for 16 hours. After this period the reaction mixture was combined with ice and the resulting heterogeneous mixture was extracted with diethyl ether (3×50 mL). The combined ethereal layer was washed with brine, dried over anhydrous MgSO4, and evaporated in vacuo to yield clean (4-bromo-2-chloro-phenyl)-acetic acid methyl ester (2.3 g, 80%). 1H-NMR (CDCl3): δ 7.56 (d, J=2.0 Hz, 1H), 7.37 (dd, J′=8.3 Hz, J″=2.0 Hz, 1H), 7.16 (d, J=8.3 Hz, 1H), 3.73 (s, 2H), 3.72 (s, 3H). After the addition was refluxed for 16 hours After this period the reaction mixture was combined with ice the resulting heterogeneous mixture was extracted with diethyl ether (3×50 mL) The combined ethereal layer was washed with brine dried over anhydrous MgSO4 evaporated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-Bromo-2-chlorophenylacetic acid methyl ester (259 g) of Reference Example 16 was dissolved in ethanol (1400 mL) and water (355 mL), calcium chloride (107 g) was added at 7° C., and the mixture was stirred for 30 min. To the reaction mixture was added sodium borohydride (73 g) by portions so that the inside temperature would not exceed 15° C. After stirring at 7° C. for 1 hr, the mixture was stirred at room temperature for 1 hr. 0.1M Hydrochloric acid (4257 mL) was added dropwise to the reaction mixture, and the reaction solvent was evaporated under reduced pressure. 0.1M Hydrochloric acid (4257 mL) was added dropwise to the residue, and 1M hydrochloric acid (3000 mL) was further added dropwise. After partitioning and extraction with ethyl acetate, the organic layer was washed with 25% brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (229 g) as a brown oil. exceed 15° C After stirring at 7° C. for 1 hr the mixture was stirred at room temperature for 1 hr the reaction solvent was evaporated under reduced pressure 0.1M Hydrochloric acid (4257 mL) was added dropwise to the residue, and 1M hydrochloric acid (3000 mL) was further added dropwise After partitioning extraction with ethyl acetate the organic layer was washed with 25% brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-bromo-2-chlorophenylacetic acid (240 g) of Reference Example 15 in N,N-dimethylformamide (3000 mL) were added potassium carbonate (399 g) and iodomethane (164 g) at 7° C., and the mixture was stirred at the same temperature for 3 hr and stirred at room temperature for 19 hr. The reaction mixture was poured into water, and partitioned and extracted with ethyl acetate. The organic layer was washed 3 times with 25% brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the title compound (259 g) as a brown oil. stirred at room temperature for 19 hr partitioned extracted with ethyl acetate The organic layer was washed 3 times with 25% brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (4-Bromo-2-chloro-phenyl)-acetonitrile (1.98 g, 8.6 mmoles) was dissolved into MeOH (50 mL) and water (5 mL), and the resulting homogeneous mixture was chilled to 0° C. To this stirring (cold) mixture was slowly (carefully) added concentrated HCl (25 mL). After the addition was complete the mixture was refluxed for 16 hours. After this period the reaction mixture was combined with ice and the resulting heterogeneous mixture was extracted with diethyl ether (3×50 mL). The combined ethereal layer was washed with brine, dried over anhydrous MgSO4, and evaporated in vacuo to yield clean (4-bromo-2-chloro-phenyl)-acetic acid methyl ester (2.3 g, 80%). 1H-NMR (CDCl3): δ 7.56 (d, J=2.0 Hz, 1H), 7.37 (dd, J′=8.3 Hz, J″=2.0 Hz, 1H), 7.16 (d, J=8.3 Hz, 1H), 3.73 (s, 2H), 3.72 (s, 3H). After the addition was refluxed for 16 hours After this period the reaction mixture was combined with ice the resulting heterogeneous mixture was extracted with diethyl ether (3×50 mL) The combined ethereal layer was washed with brine dried over anhydrous MgSO4 evaporated in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (4-Bromo-2-chloro-phenyl)-acetonitrile (1.98 g, 8.6 mmoles) was dissolved into MeOH (50 mL) and water (5 mL), and the resulting homogeneous mixture was chilled to 0° C. To this stirring (cold) mixture was slowly (carefully) added concentrated HCl (25 mL). After the addition was complete the mixture was refluxed for 16 hours. After this period the reaction mixture was combined with ice and the resulting heterogeneous mixture was extracted with diethyl ether (3×50 mL). The combined ethereal layer was washed with brine, dried over anhydrous MgSO4, and evaporated in vacuo to yield clean (4-bromo-2-chloro-phenyl)-acetic acid methyl ester (2.3 g, 80%). 1H-NMR (CDCl3): δ 7.56 (d, J=2.0 Hz, 1H), 7.37 (dd, J′=8.3 Hz, J″=2.0 Hz, 1H), 7.16 (d, J=8.3 Hz, 1H), 3.73 (s, 2H), 3.72 (s, 3H). After the addition was refluxed for 16 hours After this period the reaction mixture was combined with ice the resulting heterogeneous mixture was extracted with diethyl ether (3×50 mL) The combined ethereal layer was washed with brine dried over anhydrous MgSO4 evaporated in vacuo