1-prop-2-ynoxy-2-(trifluoromethoxy)benzene

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

Procedure: To a solution of the product of Example 6A (13.0 g, 56.1 mmol) in acetone (200 mL) was added N-chlorosuccinimide (8.99 g, 67.3 mmol) and silver acetate (0.936 g, 5.61 mmol). The reaction mixture was heated at reflux for 16 hours, cooled to ambient temperature, and the solvent removed under reduced pressure. The residue was taken up in a mixture of diethyl ether and water, and filtered to remove the silver salts. The filtrate was extracted with diethyl ether (300 mL). The combined organic layers were washed with saturated sodium bicarbonate (75 mL) and concentrated to give the title compound (12.9 g) which was used without further purification in the next step. MS (DCI) m/z 268 (M+NH4)+. The reaction mixture was heated at reflux for 16 hours the solvent removed under reduced pressure The residue was taken up in a mixture of diethyl ether and water filtered to remove the silver salts The filtrate was extracted with diethyl ether (300 mL) The combined organic layers were washed with saturated sodium bicarbonate (75 mL) concentrated

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

Procedure: To a solution of 2-trifluoromethoxyphenol (10.0 g, 56.1 mmol) in acetonitrile (120 mL) was added potassium carbonate (9.31 g, 67.4 mmol) and propargyl bromide (80% in toluene, 10.0 g, 7.70 mL, 67.4 mmol). The reaction mixture was stirred at ambient temperature for seven days, then diluted with water (150 mL) and extracted with diethyl ether (300 mL). The organic layer was separated and concentrated to obtain the title compound (13.05 g) which was used without further purification in the next step. extracted with diethyl ether (300 mL) The organic layer was separated concentrated

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

Procedure: To a solution of the product of Example 66A (13.0 g, 56.1 mmol) in acetone (200 mL) was added N-chlorosuccinimide (8.99 g, 67.3 mmol) and silver acetate (0.936 g, 5.61 mmol). The reaction was heated at reflux for 16 hours, cooled to ambient temperature, and the solvent removed under reduced pressure. The residue was taken up in a mixture of diethyl ether and water, and filtered to remove the silver salts. The filtrate was extracted with diethyl ether (300 mL). The combined organic layers were washed with saturated sodium bicarbonate (75 mL) and concentrated to give the title compound (12.85 g) which was used without further purification in the next step. 1H NMR (300 MHz, CDCl3) δ 7.30-7.24 (m, 2H), 7.15-7.09 (m, 1H), 7.01 (td, J=7.8, 1.4 Hz, 1H), 4.77 (s, 2H); MS (DCI) m/z 268 (M+NH4)+. The reaction was heated at reflux for 16 hours the solvent removed under reduced pressure The residue was taken up in a mixture of diethyl ether and water filtered to remove the silver salts The filtrate was extracted with diethyl ether (300 mL) The combined organic layers were washed with saturated sodium bicarbonate (75 mL) concentrated

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

Procedure: To a solution of 2-trifluoromethoxyphenol (10.0 g, 56.1 mmol) in acetonitrile (120 mL) was added potassium carbonate (9.31 g, 67.4 mmol) and propargyl bromide (80% in toluene, 10.0 g, 7.70 mL, 67.4 mmol). The reaction was stirred at ambient temperature for seven days, then diluted with water (150 mL) and extracted with diethyl ether (300 mL). The organic layer was separated and concentrated to obtain the title compound (13.05 g) which was used without further purification in the next step. 1H NMR (300 MHz, CDCl3) δ 7.30-7.23 (m, 2H), 7.19-7.13 (m, 1H), 7.04-6.95 (m, 1H), 4.77 (d, J=2.4 Hz, 2H), 2.53 (t, J=2.4 Hz, 1H). extracted with diethyl ether (300 mL) The organic layer was separated concentrated

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

Procedure: To a solution of the product of Example 66A (13.0 g, 56.1 mmol) in acetone (200 mL) was added N-chlorosuccinimide (8.99 g, 67.3 mmol) and silver acetate (0.936 g, 5.61 mmol). The reaction was heated at reflux for 16 hours, cooled to ambient temperature, and the solvent removed under reduced pressure. The residue was taken up in a mixture of diethyl ether and water, and filtered to remove the silver salts. The filtrate was extracted with diethyl ether (300 mL). The combined organic layers were washed with saturated sodium bicarbonate (75 mL) and concentrated to give the title compound (12.85 g) which was used without further purification in the next step. 1H NMR (300 MHz, CDCl3) δ 7.30-7.24 (m, 2H), 7.15-7.09 (m, 1H), 7.01 (td, J=7.8, 1.4 Hz, 1H), 4.77 (s, 2H); MS (DCI) m/z 268 (M+NH4)+. The reaction was heated at reflux for 16 hours the solvent removed under reduced pressure The residue was taken up in a mixture of diethyl ether and water filtered to remove the silver salts The filtrate was extracted with diethyl ether (300 mL) The combined organic layers were washed with saturated sodium bicarbonate (75 mL) concentrated

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

Procedure: To a solution of 2-trifluoromethoxyphenol (10.0 g, 56.1 mmol) in acetonitrile (120 mL) was added potassium carbonate (9.31 g, 67.4 mmol) and propargyl bromide (80% in toluene, 10.0 g, 7.70 mL, 67.4 mmol). The reaction was stirred at ambient temperature for seven days, then diluted with water (150 mL) and extracted with diethyl ether (300 mL). The organic layer was separated and concentrated to obtain the title compound (13.05 g) which was used without further purification in the next step. 1H NMR (300 MHz, CDCl3) δ 7.30-7.23 (m, 2H), 7.19-7.13 (m, 1H), 7.04-6.95 (m, 1H), 4.77 (d, J=2.4 Hz, 2H), 2.53 (t, J=2.4 Hz, 1H). extracted with diethyl ether (300 mL) The organic layer was separated concentrated

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

Procedure: To a solution of the product of Example 6A (13.0 g, 56.1 mmol) in acetone (200 mL) was added N-chlorosuccinimide (8.99 g, 67.3 mmol) and silver acetate (0.936 g, 5.61 mmol). The reaction mixture was heated at reflux for 16 hours, cooled to ambient temperature, and the solvent removed under reduced pressure. The residue was taken up in a mixture of diethyl ether and water, and filtered to remove the silver salts. The filtrate was extracted with diethyl ether (300 mL). The combined organic layers were washed with saturated sodium bicarbonate (75 mL) and concentrated to give the title compound (12.9 g) which was used without further purification in the next step. MS (DCI) m/z 268 (M+NH4)+. The reaction mixture was heated at reflux for 16 hours the solvent removed under reduced pressure The residue was taken up in a mixture of diethyl ether and water filtered to remove the silver salts The filtrate was extracted with diethyl ether (300 mL) The combined organic layers were washed with saturated sodium bicarbonate (75 mL) concentrated

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

Procedure: To a solution of 2-trifluoromethoxyphenol (10.0 g, 56.1 mmol) in acetonitrile (120 mL) was added potassium carbonate (9.31 g, 67.4 mmol) and propargyl bromide (80% in toluene, 10.0 g, 7.70 mL, 67.4 mmol). The reaction mixture was stirred at ambient temperature for seven days, then diluted with water (150 mL) and extracted with diethyl ether (300 mL). The organic layer was separated and concentrated to obtain the title compound (13.05 g) which was used without further purification in the next step. extracted with diethyl ether (300 mL) The organic layer was separated concentrated