ethyl 2-(4-bromo-2-chlorophenoxy)acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared analogously to Example 130a from ethyl (4-bromo-2-chloro-phenoxy)-acetate (Z26) and 4-fluoro-phenylboric acid.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared analogously to Example 130a from ethyl (4-bromo-2-chloro-phenoxy)-acetate (Z26) and 4-fluoro-phenylboric acid.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared analogously to Example 130a from ethyl (4-bromo-2-chloro-phenoxy)-acetate (Z26) and 4-chlorophenylboric acid.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared analogously to Example 130a from ethyl (4-bromo-2-chloro-phenoxy)-acetate (Z26) and 2-chlorophenylboric acid.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared analogously to Example 130a from ethyl (4-bromo-2-chloro-phenoxy)-acetate (Z26) and 2-chlorophenylboric acid.

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 14.5 mL (83.242 mmol) Hünig base was added to a solution of 7.800 g (37.222 mmol) 4-bromo-2-chlorophenol and 4.70 mL (41.537 mmol) ethyl bromoacetate in 100 mL DMF and the mixture was stirred for 4 h at 100° C. The reaction mixture was combined with water and exhaustively extracted with EtOAc. The combined org. phases were washed with saturated aqueous sodium bicarbonate, water and saturated aqueous NaCl, dried over sodium sulphate and evaporated down i. vac. The crude product was used in the next reaction step without any further purification. exhaustively extracted with EtOAc phases were washed with saturated aqueous sodium bicarbonate, water and saturated aqueous NaCl dried over sodium sulphate evaporated down i The crude product was used in the next reaction step without any further purification

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-chloro-phenol (2.0 g, 9.64 mmol) and anhydrous potassium carbonate (4.0 g, 28.92 mmol) in dry DMF (30 ml) was heated at 60° C. for 1 h under Ar atmosphere. The mixture was then cooled to room temperature and ethyl chloroacetate (1.24 ml, 11.57 mmol) was added through septum using syringe. The mixture was stirred overnight at room temperature and poured into water with stirring. Stirring continued for 10 min, and then partitioned between ethyl acetate and water. The organic phase washed with brine, dried (anhydrous MgSO4), and concentrated. The residue was purified by silica gel column chromatography (n-Hexane:Ethyl acetate:MeOH=15:3:1) to give (4-Bromo-2-chloro-phenoxy)-acetic acid ethyl ester as a colorless oil (2.98 (2.83) g, >100% yield). To (4-bromo-2-chloro-phenoxy)-acetic acid (132.8 mg, 0.5 mmol), 3-amino-benzamide (102.2 mg, 0.75 mmol), N-(3-dimethylaminopropyl)-N′-ethyl carbodiimide HCl (EDC) (143.8 mg, 0.75 mmol) and 1-hydroxybenzotriazole (HOBt) (101.4 mg, 0.75 mmol) in DMF (5 ml) was added N,N-diisopropylethylamine, redistilled (DIPEA) (0.13 ml, 0.75 mmol). The mixture was stirred overnight, and then partitioned between ethyl acetate and water. The organic phase was washed with brine, dried (MgSO4 anh), and concentrated. The residue was purified by silica gel flash column chromatography (CH2CH2:MeOH=10:1) to give 3-[2-(4-bromo-2-chloro-phenoxy)acetyl-amino]-benzamide as a white solid (181.4 mg, 94.6% yield). The mixture was then cooled to room temperature with stirring Stirring continued for 10 min partitioned between ethyl acetate and water The organic phase washed with brine dried (anhydrous MgSO4) concentrated The residue was purified by silica gel column chromatography (n-Hexane:Ethyl acetate:MeOH=15:3:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared analogously to Example 130a from ethyl (4-bromo-2-chloro-phenoxy)-acetate (Z26) and 4-fluoro-phenylboric acid.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared analogously to Example 130a from ethyl (4-bromo-2-chloro-phenoxy)-acetate (Z26) and 4-chlorophenylboric acid.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared analogously to Example 130a from ethyl (4-bromo-2-chloro-phenoxy)-acetate (Z26) and 2-chlorophenylboric acid.

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 14.5 mL (83.242 mmol) Hünig base was added to a solution of 7.800 g (37.222 mmol) 4-bromo-2-chlorophenol and 4.70 mL (41.537 mmol) ethyl bromoacetate in 100 mL DMF and the mixture was stirred for 4 h at 100° C. The reaction mixture was combined with water and exhaustively extracted with EtOAc. The combined org. phases were washed with saturated aqueous sodium bicarbonate, water and saturated aqueous NaCl, dried over sodium sulphate and evaporated down i. vac. The crude product was used in the next reaction step without any further purification. exhaustively extracted with EtOAc phases were washed with saturated aqueous sodium bicarbonate, water and saturated aqueous NaCl dried over sodium sulphate evaporated down i The crude product was used in the next reaction step without any further purification