ethyl 2-(3-chlorophenyl)-2,2-difluoroacetate

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 1.00 g (4.26 mmol) (3-chloro-phenyl)-difluoro-acetic acid ethyl ester (prepared according to the procedure described in WO 2006/122788) were dissolved in 100 ml of methanol and treated in an ice bath with 120 mg (0.75 mmol) of sodium borohydride. After stirring overnight the mixture was evaporated and the residue was purified by silica gel chromatography (DCM/methanol 98:2) to give 700 mg of the title compound. was evaporated the residue was purified by silica gel chromatography (DCM/methanol 98:2)

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

Procedure: 1.00 g (4.26 mmol) (3-chloro-phenyl)-difluoro-acetic acid ethyl ester (prepared according to the procedure described in WO 2006/122788) were dissolved in 100 ml of methanol and treated in an ice bath with 120 mg (0.75 mmol) of sodium borohydride. After stirring overnight the mixture was evaporated and the residue was purified by silica gel chromatography (DCM/methanol 98:2) to give 700 mg of the title compound. was evaporated the residue was purified by silica gel chromatography (DCM/methanol 98:2)

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 1.00 g (4.26 mmol) (3-chloro-phenyl)-difluoro-acetic acid ethyl ester (prepared according to the procedure described in WO 2006/122788) were dissolved in 100 ml of methanol and treated in an ice bath with 120 mg (0.75 mmol) of sodium borohydride. After stirring overnight the mixture was evaporated and the residue was purified by silica gel chromatography (DCM/methanol 98:2) to give 700 mg of the title compound. was evaporated the residue was purified by silica gel chromatography (DCM/methanol 98:2)

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

Procedure: 1.00 g (4.26 mmol) (3-chloro-phenyl)-difluoro-acetic acid ethyl ester (prepared according to the procedure described in WO 2006/122788) were dissolved in 100 ml of methanol and treated in an ice bath with 120 mg (0.75 mmol) of sodium borohydride. After stirring overnight the mixture was evaporated and the residue was purified by silica gel chromatography (DCM/methanol 98:2) to give 700 mg of the title compound. was evaporated the residue was purified by silica gel chromatography (DCM/methanol 98:2)

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

Procedure: To a solution of NH3 in MeOH (2 M, 50 mL, 100 mmol) was added (3-chlorophenyl)difluoroacetic acid ethyl ester (4.78 g, 20.4 mmol), as prepared in the preceding step. The homogeneous yellow solution was allowed to sit at room temperature for 13 h, and was then concentrated to provide 3.99 g (95%) of the title compound as a yellow powder. 1H NMR (300 MHz, DMSO-d6) δ 8.41 (br, 1H), 8.09 (br, 1H), 7.68-7.60 (m, 2H), 7.59-7.52 (m, 2H). as prepared in the preceding step was then concentrated

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

Procedure: To a mixture of copper bronze (2.93 g, 46.1 mmol) in DMSO (5.0 mL) was added ethyl bromodifluoroacetate (3.2 mL, 25 mmol) under argon at room temperature (see Sato, K. et al; Chem. Pharm. Bull. 47:1013-1016, 1999). After stirring for 1 h, 1-chloro-3-iodobenzene (2.57 mL, 20.8 mmol) was added under argon at room temperature. After shaking for 3 days, the mixture was diluted with saturated NH4Cl (50 mL) and extracted with ether (25 mL). The biphasic mixture was filtered through a pad of Celite, and the filter cake was washed with ether (25 mL). The organic layer was separated from the filtrate, and the aqueous layer was extracted with ether (25 mL). The combined organic layers were washed with saturated NH4Cl (2×15 mL) and brine (15 mL), dried (Na2SO4), and concentrated to afford the title compound (4.77 g, 97%) as a clear yellow oil. 1H NMR (300 MHz, CDCl3) δ 7.63-7.59 (m, 1H), 7.53-7.45 (m, 2H), 7.43-7.36 (m, 1H), 4.31 (q, J=7.2 Hz, 2H), 1.32 (t, J=7.2 Hz, 3H). After shaking for 3 days extracted with ether (25 mL) The biphasic mixture was filtered through a pad of Celite the filter cake was washed with ether (25 mL) The organic layer was separated from the filtrate the aqueous layer was extracted with ether (25 mL) The combined organic layers were washed with saturated NH4Cl (2×15 mL) and brine (15 mL) dried (Na2SO4) concentrated

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

Procedure: 1.00 g (4.26 mmol) (3-chloro-phenyl)-difluoro-acetic acid ethyl ester (prepared according to the procedure described in WO 2006/122788) were dissolved in 100 ml of methanol and treated in an ice bath with 120 mg (0.75 mmol) of sodium borohydride. After stirring overnight the mixture was evaporated and the residue was purified by silica gel chromatography (DCM/methanol 98:2) to give 700 mg of the title compound. was evaporated the residue was purified by silica gel chromatography (DCM/methanol 98:2)

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

Procedure: 1.00 g (4.26 mmol) (3-chloro-phenyl)-difluoro-acetic acid ethyl ester (prepared according to the procedure described in WO 2006/122788) were dissolved in 100 ml of methanol and treated in an ice bath with 120 mg (0.75 mmol) of sodium borohydride. After stirring overnight the mixture was evaporated and the residue was purified by silica gel chromatography (DCM/methanol 98:2) to give 700 mg of the title compound. was evaporated the residue was purified by silica gel chromatography (DCM/methanol 98:2)

Conditions: temp:0.00; pressure:0.00; stir: