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

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

Procedure: Obtained from Intermediate 48 (21.1 g, 75.8 mmol) by the procedure described in Intermediate 2. The title compound was obtained (17.2 g, 96%) as oil.

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

Procedure: Lithium hydroxide (0.13 g, 3.12 mmol) is added to a solution of (3-bromo-phenyl)-difluoro-acetic acid ethyl ester (0.29 g, 1.04 mmol) in methanol/water (8 mL, 3:1) and the reaction mixture is stirred overnight at room temperature. The mixture is diluted with water and volatiles are removed in vacuo. The aqueous is extracted once with diethyl ether, acidified to pH 2, and extracted twice with ethyl acetate. The combined extracts are dried over magnesium sulfate, filtered and concentrated in vacuo to afford (3-bromo-phenyl)-difluoro-acetic acid (250 mg), which is used in the next step without further purification. LCMS: RT=2.26 minutes; MS: 249, 251(M−H). are removed in vacuo The aqueous is extracted once with diethyl ether extracted twice with ethyl acetate The combined extracts are dried over magnesium sulfate filtered concentrated in vacuo

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

Procedure: Lithium hydroxide (0.13 g, 3.12 mmol) is added to a solution of (3-bromo-phenyl)-difluoro-acetic acid ethyl ester (0.29 g, 1.04 mmol) in methanol/water (8 mL, 3:1) and the reaction mixture is stirred overnight at room temperature. The mixture is diluted with water and volatiles are removed in vacuo. The aqueous is extracted once with diethyl ether, acidified to pH 2, and extracted twice with ethyl acetate. The combined extracts are dried over magnesium sulfate, filtered and concentrated in vacuo to afford (3-bromo-phenyl)-difluoro-acetic acid (250 mg), which is used in the next step without further purification. LCMS: RT=2.26 minutes; MS: 249, 251(M−H). are removed in vacuo The aqueous is extracted once with diethyl ether extracted twice with ethyl acetate The combined extracts are dried over magnesium sulfate filtered concentrated in vacuo

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

Procedure: Lithium hydroxide (0.13 g, 3.12 mmol) is added to a solution of (3-bromo-phenyl)-difluoro-acetic acid ethyl ester (0.29 g, 1.04 mmol) in methanol/water (8 mL, 3:1) and the reaction mixture is stirred overnight at room temperature. The mixture is diluted with water and volatiles are removed in vacuo. The aqueous is extracted once with diethyl ether, acidified to pH 2, and extracted twice with ethyl acetate. The combined extracts are dried over magnesium sulfate, filtered and concentrated in vacuo to afford (3-bromo-phenyl)-difluoro-acetic acid (250 mg), which is used in the next step without further purification. LCMS: RT=2.26 minutes; MS: 249, 251(M−H). are removed in vacuo The aqueous is extracted once with diethyl ether extracted twice with ethyl acetate The combined extracts are dried over magnesium sulfate filtered concentrated in vacuo

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

Procedure: Obtained from Intermediate 48 (21.1 g, 75.6 mmol) by the procedure described in Intermediate 2. The title compound was obtained (17.2 g, 96%) as oil.

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

Procedure: Obtained from Intermediate 48 (21.1 g, 75.8 mmol) by the procedure described in Intermediate 2. The title compound was obtained (17.2 g, 96%) as oil.

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

Procedure: Lithium hydroxide (0.13 g, 3.12 mmol) is added to a solution of (3-bromo-phenyl)-difluoro-acetic acid ethyl ester (0.29 g, 1.04 mmol) in methanol/water (8 mL, 3:1) and the reaction mixture is stirred overnight at room temperature. The mixture is diluted with water and volatiles are removed in vacuo. The aqueous is extracted once with diethyl ether, acidified to pH 2, and extracted twice with ethyl acetate. The combined extracts are dried over magnesium sulfate, filtered and concentrated in vacuo to afford (3-bromo-phenyl)-difluoro-acetic acid (250 mg), which is used in the next step without further purification. LCMS: RT=2.26 minutes; MS: 249, 251(M−H). are removed in vacuo The aqueous is extracted once with diethyl ether extracted twice with ethyl acetate The combined extracts are dried over magnesium sulfate filtered concentrated in vacuo