prop-2-ynyl benzoate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of prop-2-yn-1-yl benzoate (26.0 g, 162 mmol) in chloroform (598 mL) was treated with triethylamine (11.3 mL, 81.2 mmol) and acetaldoxime (14.4 g, 244 mmol). The reaction mixture was cooled to 0° C., treated with sodium hypochlorite (551 mL, 487 mmol) (commercial grade ˜5% aqueous), and stirred overnight at room temperature. The layers were separated and the aqueous layer was extracted with dichloromethane (2×200 mL). The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered, and concentrated to give the crude product. Purification by flash column chromatography (100% hexanes to 30% ethyl acetate/hexanes) gave the desired product (20.1 g, 57%). LCMS calculated for C12H12NO3 (M+H)+: m/z=218.1. found: 218.1. The layers were separated the aqueous layer was extracted with dichloromethane (2×200 mL) The combined organic layers were washed with water and brine dried over magnesium sulfate filtered concentrated to give the crude product Purification by flash column chromatography (100% hexanes to 30% ethyl acetate/hexanes)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of prop-2-yn-1-yl benzoate (26.0 g, 162 mmol) in chloroform (598 mL) was treated with triethylamine (11.3 mL, 81.2 mmol) and acetaldoxime (14.4 g, 244 mmol). The reaction mixture was cooled to 0° C., treated with sodium hypochlorite (551 mL, 487 mmol) (commercial grade ˜5% aqueous), and stirred overnight at room temperature. The layers were separated and the aqueous layer was extracted with dichloromethane (2×200 mL). The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered, and concentrated to give the crude product. Purification by flash column chromatography (100% hexanes to 30% ethyl acetate/hexanes) gave the desired product (20.1 g, 57%). LCMS calculated for C12H12NO3 (M+H)+: m/z=218.1. found: 218.1. The layers were separated the aqueous layer was extracted with dichloromethane (2×200 mL) The combined organic layers were washed with water and brine dried over magnesium sulfate filtered concentrated to give the crude product Purification by flash column chromatography (100% hexanes to 30% ethyl acetate/hexanes)

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

Procedure: To a solution of chloroform, Et3N (0.435 ml, 3.12 mmol), prop-2-ynyl benzoate (1 g, 6.24 mmol), and (E)-acetaldehyde oxime (0.571 ml, 9.37 mmol) at 0° C. was added bleach (23.12 ml, 18.73 mmol). The reaction was stirred overnight before the layers were separated and the aqueous extracted with DCM. The combined organics were dried over Na2SO4, filtered, and concentrated. The crude residue was purified via Biotage (EtOAc/hex) to afford (3-methylisoxazol-5-yl)methyl benzoate. m/z (ESI) 218 [M+H]+. were separated the aqueous extracted with DCM The combined organics were dried over Na2SO4 filtered concentrated The crude residue was purified via Biotage (EtOAc/hex)

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

Procedure: To a solution of chloroform, Et3N (0.435 mL, 3.12 mmol), prop-2-ynyl benzoate (1 g, 6.24 mmol), and (E)-acetaldehyde oxime (0.571 mL, 9.37 mmol) at 0° C. was added bleach (23.12 mL, 18.73 mmol). The reaction was stirred overnight before the layers were separated and the aqueous extracted with DCM. The combined organics were dried over Na2SO4, filtered, and concentrated. The crude residue was purified via Biotage (EtOAc/hex) to afford (3-methylisoxazol-5-yl)methyl benzoate. LC/MS m/z 218 [M+H]+. were separated the aqueous extracted with DCM The combined organics were dried over Na2SO4 filtered concentrated The crude residue was purified via Biotage (EtOAc/hex)

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

Procedure: To a solution of chloroform, Et3N (0.435 mL, 3.12 mmol), prop-2-ynyl benzoate (1 g, 6.24 mmol), and (E)-acetaldehyde oxime (0.571 mL, 9.37 mmol) at 0° C. was added bleach (23.12 mL, 18.73 mmol). The reaction was stirred overnight before the layers were separated and the aqueous extracted with DCM. The combined organics were dried over Na2SO4, filtered, and concentrated. The crude residue was purified via Biotage (EtOAc/hex) to afford (3-methylisoxazol-5-yl)methyl benzoate. LC/MS m/z 218 [M+H]+. were separated the aqueous extracted with DCM The combined organics were dried over Na2SO4 filtered concentrated The crude residue was purified via Biotage (EtOAc/hex)

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

Procedure: To a solution of prop-2-yn-1-ol (3.63 mL, 62.4 mmol), DCM (180 mL), and Et3N (17.40 mL, 125 mmol) at 0° C. were added benzoyl chloride (7.25 mL, 62.4 mmol) and DMAP (0.381 g, 3.12 mmol). The reaction was stirred while warming to room temperature overnight. The reaction was diluted with water and the layers separated. The aqueous was extracted with DCM and the combined organics were dried over Na2SO4, filtered, and concentrated to afford prop-2-yn-1-yl benzoate which was used in subsequent reactions without further purification. LC/MS m/z 161 [M+H]+. the layers separated The aqueous was extracted with DCM the combined organics were dried over Na2SO4 filtered concentrated

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

Procedure: To a solution of prop-2-yn-1-ol (3.63 mL, 62.4 mmol), DCM (180 mL), and Et3N (17.40 mL, 125 mmol) at 0° C. were added benzoyl chloride (7.25 mL, 62.4 mmol) and DMAP (0.381 g, 3.12 mmol). The reaction was stirred while warming to room temperature overnight. The reaction was diluted with water and the layers separated. The aqueous was extracted with DCM and the combined organics were dried over Na2SO4, filtered, and concentrated to afford prop-2-yn-1-yl benzoate which was used in subsequent reactions without further purification. LC/MS m/z 161 [M+H]+. the layers separated The aqueous was extracted with DCM the combined organics were dried over Na2SO4 filtered concentrated

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

Procedure: A solution of 2-thiophenecarbonyl chloride (549 mg, 3.75 mmol) in anhydrous dioxane (15 mL) was bubbled with argon for 10 minutes. Triethylamine (1.31 mL, 9.36 mmol) was added and the bubbling was maintained for 5 minutes. Bis(triphenylphosphine)palladium(II) dichloride (88 mg, 0.12 mmol), copper iodide (48 mg, 0.25 mmol) and propargyl benzoate (0.45 mL, 3.12 mmol) were added, and the reaction mixture was stirred for 1 hour at room temperature, under argon atmosphere. The solution was filtered and water (20 mL) was added to the filtrate. Layers were separated, and the aqueous layer was extracted with dichloromethane (2×20 mL). The combined organic layers were washed with a saturated solution of sodium hydrogenocarbonate (20 mL), dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 100/0 to 95/5) to provide 4-oxo-4-(thiophen-2-yl)but-2-yn-1-yl benzoate (3a) (333 mg, 1.23 mmol, 39%). the bubbling was maintained for 5 minutes The solution was filtered water (20 mL) was added to the filtrate Layers were separated the aqueous layer was extracted with dichloromethane (2×20 mL) The combined organic layers were washed with a saturated solution of sodium hydrogenocarbonate (20 mL) dried over sodium sulfate concentrated in vacuo The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 100/0 to 95/5)

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

Procedure: To a solution of prop-2-yn-1-ol (3.63 ml, 62.4 mmol), DCM (180 ml), and Et3N (17.40 ml, 125 mmol) at 0° C. were added benzoyl chloride (7.25 ml, 62.4 mmol) and DMAP (0.381 g, 3.12 mmol). The reaction was stirred while warming to room temperature overnight. The reaction was diluted with water and the layers separated. The aqueous was extracted with DCM and the combined organics were dried over Na2SO4, filtered, and concentrated to afford prop-2-yn-1-yl benzoate which was used in subsequent reactions without further purification. m/z (ESI) 161 [M+H]+. the layers separated The aqueous was extracted with DCM the combined organics were dried over Na2SO4 filtered concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of prop-2-yn-1-yl benzoate (26.0 g, 162 mmol) in chloroform (598 mL) was treated with triethylamine (11.3 mL, 81.2 mmol) and acetaldoxime (14.4 g, 244 mmol). The reaction mixture was cooled to 0° C., treated with sodium hypochlorite (551 mL, 487 mmol) (commercial grade ˜5% aqueous), and stirred overnight at room temperature. The layers were separated and the aqueous layer was extracted with dichloromethane (2×200 mL). The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered, and concentrated to give the crude product. Purification by flash column chromatography (100% hexanes to 30% ethyl acetate/hexanes) gave the desired product (20.1 g, 57%). LCMS calculated for C12H12NO3 (M+H)+: m/z=218.1. found: 218.1. The layers were separated the aqueous layer was extracted with dichloromethane (2×200 mL) The combined organic layers were washed with water and brine dried over magnesium sulfate filtered concentrated to give the crude product Purification by flash column chromatography (100% hexanes to 30% ethyl acetate/hexanes)