2-(5-chloro-2-methoxyphenyl)ethynyl-trimethylsilane

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

Procedure: Add a solution of potassium hydroxide (3.28 g, 58.5 mmol) in water (30 mL) dropwise over 25 minutes to a stirred solution of (5-chloro-2-methoxy-phenylethynyl)-trimethylsilane (13.7 g, 57.4 mmol) in methanol (275 mL) and stir at room temperature for 2 hours. Concentrate, add brine to residue, and extract with EtOAc (×2). Dry organic layer over MgSO4 and concentrate to get 13 g of a black oil. Adsorb on SiO2 and purify the residue by flash chromatography on silica gel eluting with 0-5% EtOAc/hexanes to afford the title compound (8.98 g, 94%). Concentrate add brine to residue extract with EtOAc (×2) Dry organic layer over MgSO4 and concentrate

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

Procedure: Add a solution of potassium hydroxide (3.28 g, 58.5 mmol) in water (30 mL) dropwise over 25 minutes to a stirred solution of (5-chloro-2-methoxy-phenylethynyl)-trimethylsilane (13.7 g, 57.4 mmol) in methanol (275 mL) and stir at room temperature for 2 hours. Concentrate, add brine to residue, and extract with EtOAc (×2). Dry organic layer over MgSO4 and concentrate to get 13 g of a black oil. Adsorb on SiO2 and purify the residue by flash chromatography on silica gel eluting with 0-5% EtOAc/hexanes to afford the title compound (8.98 g, 94%). Concentrate add brine to residue extract with EtOAc (×2) Dry organic layer over MgSO4 and concentrate

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: ((5-chloro-2-methoxyphenyl)ethynyl)trimethylsilane (0.4 g, 1.7 mmol) was dissolved in MeOH (1 mL), K2CO3 (0.69 g, 5 mol) was added to it. Then the mixture was stirred at 25° C. for 1 hour, and added to H2O (50 mL). The mixture was extracted with ethyl acetate and washed with brine, dried over Na2SO4. After the combined organic layers were concentrated, the resulting residue was purified using prep-TLC (petroleum ether:EtOAc=10:1) to provide the product of 4-chloro-2-ethynyl-1-methoxybenzene (0.25 g, yield: 80%). 1H-NMR (CDCl3, 400 MHz) δ 7.43 (s, 1H), 7.28˜7.29 (m, 1H), 6.81˜6.85 (m, 1H), 3.89 (s, 3H), 3.34 (s, 1H). MS (M+H)+: 167/169. The mixture was extracted with ethyl acetate washed with brine dried over Na2SO4 After the combined organic layers were concentrated the resulting residue was purified

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-bromo-4-chloro-1-methoxybenzene (1 g, 4.5 mmol), CuI (43 mg, 0.23 mmol), Pd(PPh3)2Cl2 (0.16 g, 0.23 mmol) in NEt3 (10 mL) was degassed, Then ethynyltrimethylsilane (0.5 g, 5 mmol) was added to the solution, the mixture was stirred at 80° C. for 6 hours. Then the mixture was cooled to 25° C., and added to H2O (50 mL). The mixture was extracted with ethyl acetate and washed with brine, dried over Na2SO4. After the combined organic layers were concentrated, the resulting residue was purified using prep-TLC (petroleum ether:EtOAc=10:1) to provide the product of ((5-chloro-2-methoxyphenyl)ethynyl)trimethylsilane (1 g, yield: 90%). 1H-NMR (CDCl3, 400 MHz) δ 7.40 (s, 1H), 7.21˜7.23 (m, 1H), 6.76˜6.78 (d, J=9.2 Hz, 1H), 3.86 (s, 3H), 0.26 (s, 9H). MS (M+H)+: 239/241 was degassed Then the mixture was cooled to 25° C. The mixture was extracted with ethyl acetate washed with brine dried over Na2SO4 After the combined organic layers were concentrated the resulting residue was purified

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

Procedure: Add a solution of potassium hydroxide (3.28 g, 58.5 mmol) in water (30 mL) dropwise over 25 minutes to a stirred solution of (5-chloro-2-methoxy-phenylethynyl)-trimethylsilane (13.7 g, 57.4 mmol) in methanol (275 mL) and stir at room temperature for 2 hours. Concentrate, add brine to residue, and extract with EtOAc (×2). Dry organic layer over MgSO4 and concentrate to get 13 g of a black oil. Adsorb on SiO2 and purify the residue by flash chromatography on silica gel eluting with 0-5% EtOAc/hexanes to afford the title compound (8.98 g, 94%). Concentrate add brine to residue extract with EtOAc (×2) Dry organic layer over MgSO4 and concentrate

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

Procedure: Add a solution of potassium hydroxide (3.28 g, 58.5 mmol) in water (30 mL) dropwise over 25 minutes to a stirred solution of (5-chloro-2-methoxy-phenylethynyl)-trimethylsilane (13.7 g, 57.4 mmol) in methanol (275 mL) and stir at room temperature for 2 hours. Concentrate, add brine to residue, and extract with EtOAc (×2). Dry organic layer over MgSO4 and concentrate to get 13 g of a black oil. Adsorb on SiO2 and purify the residue by flash chromatography on silica gel eluting with 0-5% EtOAc/hexanes to afford the title compound (8.98 g, 94%). Concentrate add brine to residue extract with EtOAc (×2) Dry organic layer over MgSO4 and concentrate

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

Procedure: Add a solution of potassium hydroxide (3.28 g, 58.5 mmol) in water (30 mL) dropwise over 25 minutes to a stirred solution of (5-chloro-2-methoxy-phenylethynyl)-trimethylsilane (13.7 g, 57.4 mmol) in methanol (275 mL) and stir at room temperature for 2 hours. Concentrate, add brine to residue, and extract with EtOAc (×2). Dry organic layer over MgSO4 and concentrate to get 13 g of a black oil. Adsorb on SiO2 and purify the residue by flash chromatography on silica gel eluting with 0-5% EtOAc/hexanes to afford the title compound (8.98 g, 94%). Concentrate add brine to residue extract with EtOAc (×2) Dry organic layer over MgSO4 and concentrate