pent-3-yn-2-ol

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

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

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

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

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 50 ml RBF was charged with 3-pentyn-2-ol (2.063 ml, 22.08 mmol) in DMF (10 ml) and potassium t-butoxide (1.24 g, 11.04 mmol) was added portionwise while stirring (cooling in water bath). The mixture was stirred at room temperature for 10 min until all t-BuOK went into solution, then 5-chloropyrazine-2-carboxylic acid (500 mg, 3.15 mmol) was added in portions and the resulting brown suspension was heated at 75° C. for 45 min. The mixture was cooled to room temperature and diluted with water (˜20 ml) until all solids dissolved, then acidified with 2M HCl solution (˜5.5 ml) to pH 2. The resulting solution was extracted with EtOAc, organic layer was washed with water twice then with brine, filtered through pad of celite and concentrated in vacuo. The resulting suspension was diluted with 3 ml heptane/EtOAc (20:1) mixture then filtered. The solid was washed with heptane and dried in vacuo to afford 5-(pent-3-yn-2-yloxy)pyrazine-2-carboxylic acid (424 mg, 2.056 mmol, 65.2% yield) as tan solid. LC/MS (ESI+) m/z=207 (M+H). was added portionwise The mixture was cooled to room temperature dissolved The resulting solution was extracted with EtOAc, organic layer was washed with water twice with brine, filtered through pad of celite concentrated in vacuo The resulting suspension was diluted with 3 ml heptane/EtOAc (20:1) mixture then filtered The solid was washed with heptane dried in vacuo

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 50 ml RBF was charged with 3-pentyn-2-ol (2.063 ml, 22.08 mmol) in DMF (10 ml) and potassium t-butoxide (1.24 g, 11.04 mmol) was added portionwise while stirring (cooling in water bath). The mixture was stirred at room temperature for 10 min until all t-BuOK went into solution, then 5-chloropyrazine-2-carboxylic acid (500 mg, 3.15 mmol) was added in portions and the resulting brown suspension was heated at 75° C. for 45 min. The mixture was cooled to room temperature and diluted with water (˜20 ml) until all solids dissolved, then acidified with 2M HCl solution (˜5.5 ml) to pH 2. The resulting solution was extracted with EtOAc, organic layer was washed with water twice then with brine, filtered through pad of celite and concentrated in vacuo. The resulting suspension was diluted with 3 ml heptane/EtOAc (20:1) mixture then filtered. The solid was washed with heptane and dried in vacuo to afford 5-(pent-3-yn-2-yloxy)pyrazine-2-carboxylic acid (424 mg, 2.056 mmol, 65.2% yield) as tan solid. LC/MS (ESI+) m/z=207 (M+H). was added portionwise The mixture was cooled to room temperature dissolved The resulting solution was extracted with EtOAc, organic layer was washed with water twice with brine, filtered through pad of celite concentrated in vacuo The resulting suspension was diluted with 3 ml heptane/EtOAc (20:1) mixture then filtered The solid was washed with heptane dried in vacuo

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

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

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

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

Procedure: To a solution of 2-nitro-4-fluorophenol (1.6 g, 10.2 mmol) in tetrahydrofuran (32 mL), chloromethyl methyl ether (1.23 g, 15.3 mmol) and di-isopropyl ethyl amine (2.66 mL, 15.3 mmol) were added at room temperature, and the resulting mixture was stirred at room temperature for 1 hour. Upon the completion of the reaction, saturated ammonium chloride aqueous solution was added thereto, the resulting solution was extracted with ethyl acetate, washed with saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. Sodium hydride (553 mg, 12.3 mmol) and 1-methyl-2-butyn-1-ol (1.23 mL, 12.7 mmol) were added to the solution of the resulting mixture in dimethylacetamide (17 mL) at 0° C., and the resulting mixture was stirred for 7 hours. Upon the completion of the reaction, saturated ammonium chloride aqueous solution was added thereto, the resulting solution was extracted with ethyl acetate, washed with saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. The resulting mixture was purified by silica gel column (hexane/ethyl acetate=5/1) and the aimed product was obtained (yield: 94%). was added the resulting solution was extracted with ethyl acetate washed with saturated sodium chloride solution dried over magnesium sulfate concentrated the resulting mixture was stirred for 7 hours was added the resulting solution was extracted with ethyl acetate washed with saturated sodium chloride solution dried over magnesium sulfate concentrated The resulting mixture was purified by silica gel column (hexane/ethyl acetate=5/1)

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

Procedure: To a solution of 2-nitro-4-fluorophenol (1.6 g, 10.2 mmol) in tetrahydrofuran (32 mL), chloromethyl methyl ether (1.23 g, 15.3 mmol) and di-isopropyl ethyl amine (2.66 mL, 15.3 mmol) were added at room temperature, and the resulting mixture was stirred at room temperature for 1 hour. Upon the completion of the reaction, saturated ammonium chloride aqueous solution was added thereto, the resulting solution was extracted with ethyl acetate, washed with saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. Sodium hydride (553 mg, 12.3 mmol) and 1-methyl-2-butyn-1-ol (1.23 mL, 12.7 mmol) were added to the solution of the resulting mixture in dimethylacetamide (17 mL) at 0° C., and the resulting mixture was stirred for 7 hours. Upon the completion of the reaction, saturated ammonium chloride aqueous solution was added thereto, the resulting solution was extracted with ethyl acetate, washed with saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. The resulting mixture was purified by silica gel column (hexane/ethyl acetate=5/1) and the aimed product was obtained (yield: 94%). was added the resulting solution was extracted with ethyl acetate washed with saturated sodium chloride solution dried over magnesium sulfate concentrated the resulting mixture was stirred for 7 hours was added the resulting solution was extracted with ethyl acetate washed with saturated sodium chloride solution dried over magnesium sulfate concentrated The resulting mixture was purified by silica gel column (hexane/ethyl acetate=5/1)

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

Procedure: To a solution of 2-nitro-4-fluorophenol (1.6 g, 10.2 mmol) in tetrahydrofuran (32 mL), chloromethyl methyl ether (1.23 g, 15.3 mmol) and di-isopropyl ethyl amine (2.66 mL, 15.3 mmol) were added at room temperature, and the resulting mixture was stirred at room temperature for 1 hour. Upon the completion of the reaction, saturated ammonium chloride aqueous solution was added thereto, the resulting solution was extracted with ethyl acetate, washed with saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. Sodium hydride (553 mg, 12.3 mmol) and 1-methyl-2-butyn-1-ol (1.23 mL, 12.7 mmol) were added to the solution of the resulting mixture in dimethylacetamide (17 mL) at 0° C., and the resulting mixture was stirred for 7 hours. Upon the completion of the reaction, saturated ammonium chloride aqueous solution was added thereto, the resulting solution was extracted with ethyl acetate, washed with saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. The resulting mixture was purified by silica gel column (hexane/ethyl acetate=5/1) and the aimed product was obtained (yield: 94%). was added the resulting solution was extracted with ethyl acetate washed with saturated sodium chloride solution dried over magnesium sulfate concentrated the resulting mixture was stirred for 7 hours was added the resulting solution was extracted with ethyl acetate washed with saturated sodium chloride solution dried over magnesium sulfate concentrated The resulting mixture was purified by silica gel column (hexane/ethyl acetate=5/1)