benzyl prop-2-ynoate

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 6.42 g (40.1 mmol) of benzyl propiolate from step A above in 25 ml of anhydrous THF was added 0.93 g (0.80 mmol) of tetrakis(triphenylphosphine)palladium(0) followed by a solution of 12.6 g (42.1 mmol) of tributyltin hydride in 25 mL of anhydrous THF over 15 min. After stirring at room temperature overnight the solvent was removed under reduced pressure. The residue was filtered through a pad of Celite® which was then washed with hexanes. The filtrate was concentrated in vacuo and the crude product was purified by silica gel chromatography eluting with a 0-15% ethyl acetate in hexane gradient to afford the title compound as a colorless oil (13 g, 73%). 1H NMR (CDCl3, 500 MHz) δ 7.39 (m, 5H), 6.99 (d, J=2.7 Hz, 1H), 5.98 (d, J=2.7 Hz, 1H), 5.20 (s, 2H), 1.47 (m, 6H), 1.30 (m, 6H), 0.96 (m, 6H), 0.89 (t, J=7.4 Hz, 9H). was removed under reduced pressure The residue was filtered through a pad of Celite® which was then washed with hexanes The filtrate was concentrated in vacuo the crude product was purified by silica gel chromatography eluting with a 0-15% ethyl acetate in hexane gradient

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

Procedure: To a solution of 6.42 g (40.1 mmol) of benzyl propiolate from step A above in 25 ml of anhydrous THF was added 0.93 g (0.80 mmol) of tetrakis(triphenylphosphine)palladium(0) followed by a solution of 12.6 g (42.1 mmol) of tributyltin hydride in 25 mL of anhydrous THF over 15 min. After stirring at room temperature overnight the solvent was removed under reduced pressure. The residue was filtered through a pad of Celite® which was then washed with hexanes. The filtrate was concentrated in vacuo and the crude product was purified by silica gel chromatography eluting with a 0-15% ethyl acetate in hexane gradient to afford the title compound as a colorless oil (13 g, 73%). 1H NMR (CDCl3, 500 MHz) δ 7.39 (m, 5H), 6.99 (d, J=2.7 Hz, 1H), 5.98 (d, J=2.7 Hz, 1H), 5.20 (s, 2H), 1.47 (m, 6H), 1.30 (m, 6H), 0.96 (m, 6H), 0.89 (t, J=7.4 Hz, 9H). was removed under reduced pressure The residue was filtered through a pad of Celite® which was then washed with hexanes The filtrate was concentrated in vacuo the crude product was purified by silica gel chromatography eluting with a 0-15% ethyl acetate in hexane gradient

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

Procedure: To a solution of 17.0 g (233 mmol) of propiolic acid in 600 mL of anhydrous DMF was added 39.9 g (233 mmol) of benzyl bromide followed by portionwise addition of 76.0 g (233 mmol) of Cs2CO3. After stirring at room temperature for 24 h, the reaction was quenched with a saturated aqueous ammonium chloride solution and extracted with EtOAc (3×200 mL). The combined extracts were washed with water then brine and dried over anhydrous sodium sulfate. The mixture was then filtered through a silica gel pad washing with hexanes, and the filtrate was evaporated under reduced pressure to afford a crude product. The crude product was purified by silica gel chromatography eluting with a 0-20% ethyl acetate in hexane gradient to afford the title compound as a colorless oil (13.8 g, 35%). 1H NMR (CDCl3, 500 MHz) δ 7.41 (m, 5H), 5.25 (s, 2H), 2.92 (s, 1H). the reaction was quenched with a saturated aqueous ammonium chloride solution extracted with EtOAc (3×200 mL) The combined extracts were washed with water brine and dried over anhydrous sodium sulfate The mixture was then filtered through a silica gel pad washing with hexanes the filtrate was evaporated under reduced pressure to afford a crude product The crude product was purified by silica gel chromatography eluting with a 0-20% ethyl acetate in hexane gradient

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

Procedure: To a solution of 17.0 g (233 mmol) of propiolic acid in 600 mL of anhydrous DMF was added 39.9 g (233 mmol) of benzyl bromide followed by portionwise addition of 76.0 g (233 mmol) of Cs2CO3. After stirring at room temperature for 24 h, the reaction was quenched with a saturated aqueous ammonium chloride solution and extracted with EtOAc (3×200 mL). The combined extracts were washed with water then brine and dried over anhydrous sodium sulfate. The mixture was then filtered through a silica gel pad washing with hexanes, and the filtrate was evaporated under reduced pressure to afford a crude product. The crude product was purified by silica gel chromatography eluting with a 0-20% ethyl acetate in hexane gradient to afford the title compound as a colorless oil (13.8 g, 35%). 1H NMR (CDCl3, 500 MHz) δ 7.41 (m, 5H), 5.25 (s, 2H), 2.92 (s, 1H). the reaction was quenched with a saturated aqueous ammonium chloride solution extracted with EtOAc (3×200 mL) The combined extracts were washed with water brine and dried over anhydrous sodium sulfate The mixture was then filtered through a silica gel pad washing with hexanes the filtrate was evaporated under reduced pressure to afford a crude product The crude product was purified by silica gel chromatography eluting with a 0-20% ethyl acetate in hexane gradient

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

Procedure: To a solution of 6.42 g (40.1 mmol) of benzyl propiolate from step A above in 25 ml of anhydrous THF was added 0.93 g (0.80 mmol) of tetrakis(triphenylphosphine)palladium(0) followed by a solution of 12.6 g (42.1 mmol) of tributyltin hydride in 25 mL of anhydrous THF over 15 min. After stirring at room temperature overnight the solvent was removed under reduced pressure. The residue was filtered through a pad of Celite® which was then washed with hexanes. The filtrate was concentrated in vacuo and the crude product was purified by silica gel chromatography eluting with a 0-15% ethyl acetate in hexane gradient to afford the title compound as a colorless oil (13 g, 73%). 1H NMR (CDCl3, 500 MHz) δ 7.39 (m, 5H), 6.99 (d, J=2.7 Hz, 1H), 5.98 (d, J=2.7 Hz, 1H), 5.20 (s, 2H), 1.47 (m, 6H), 1.30 (m, 6H), 0.96 (m, 6H), 0.89 (t, J=7.4 Hz, 9H). was removed under reduced pressure The residue was filtered through a pad of Celite® which was then washed with hexanes The filtrate was concentrated in vacuo the crude product was purified by silica gel chromatography eluting with a 0-15% ethyl acetate in hexane gradient

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

Procedure: To a solution of 6.42 g (40.1 mmol) of benzyl propiolate from step A above in 25 ml of anhydrous THF was added 0.93 g (0.80 mmol) of tetrakis(triphenylphosphine)palladium(0) followed by a solution of 12.6 g (42.1 mmol) of tributyltin hydride in 25 mL of anhydrous THF over 15 min. After stirring at room temperature overnight the solvent was removed under reduced pressure. The residue was filtered through a pad of Celite® which was then washed with hexanes. The filtrate was concentrated in vacuo and the crude product was purified by silica gel chromatography eluting with a 0-15% ethyl acetate in hexane gradient to afford the title compound as a colorless oil (13 g, 73%). 1H NMR (CDCl3, 500 MHz) δ 7.39 (m, 5H), 6.99 (d, J=2.7 Hz, 1H), 5.98 (d, J=2.7 Hz, 1H), 5.20 (s, 2H), 1.47 (m, 6H), 1.30 (m, 6H), 0.96 (m, 6H), 0.89 (t, J=7.4 Hz, 9H). was removed under reduced pressure The residue was filtered through a pad of Celite® which was then washed with hexanes The filtrate was concentrated in vacuo the crude product was purified by silica gel chromatography eluting with a 0-15% ethyl acetate in hexane gradient

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

Procedure: To a solution of 17.0 g (233 mmol) of propiolic acid in 600 mL of anhydrous DMF was added 39.9 g (233 mmol) of benzyl bromide followed by portionwise addition of 76.0 g (233 mmol) of Cs2CO3. After stirring at room temperature for 24 h, the reaction was quenched with a saturated aqueous ammonium chloride solution and extracted with EtOAc (3×200 mL). The combined extracts were washed with water then brine and dried over anhydrous sodium sulfate. The mixture was then filtered through a silica gel pad washing with hexanes, and the filtrate was evaporated under reduced pressure to afford a crude product. The crude product was purified by silica gel chromatography eluting with a 0-20% ethyl acetate in hexane gradient to afford the title compound as a colorless oil (13.8 g, 35%). 1H NMR (CDCl3, 500 MHz) δ 7.41 (m, 5H), 5.25 (s, 2H), 2.92 (s, 1H). the reaction was quenched with a saturated aqueous ammonium chloride solution extracted with EtOAc (3×200 mL) The combined extracts were washed with water brine and dried over anhydrous sodium sulfate The mixture was then filtered through a silica gel pad washing with hexanes the filtrate was evaporated under reduced pressure to afford a crude product The crude product was purified by silica gel chromatography eluting with a 0-20% ethyl acetate in hexane gradient

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

Procedure: To a solution of 2,3-methylenediexyphenol (27 g) and N-methyl morpholine (19.6 g) in THF (100 ml) was added benzyl propiolate (38 g) over a period of 30 minutes with cooling. After the addition was complete the reaction was stirred at room temperature for 1.5 hours followed by concentration. The residue was taken up into Et2O (500 ml), washed with 10% HCl (2×100 ml), dried over MgSO4, filtered and concentrated. This material was subjected to hydrogenation with 10% Pd/C in methanol at 4 atm. The reaction was filtered and concentrated. The resulting saturated acid was dissolved into methanesulfonic acid (350 ml) and stirred for 24 hours. The reaction was poured onto ice and extracted with CH2Cl2. The organic layer was washed with saturated Na2CO3, dried over MgSO4, filtered and concentrated to provide the desired material. with cooling After the addition followed by concentration washed with 10% HCl (2×100 ml) dried over MgSO4 filtered concentrated The reaction was filtered concentrated The resulting saturated acid was dissolved into methanesulfonic acid (350 ml) stirred for 24 hours The reaction was poured onto ice extracted with CH2Cl2 The organic layer was washed with saturated Na2CO3 dried over MgSO4 filtered concentrated

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirring mixture of 2-propynoic acid phenylmethyl ester (2.46 g, 15.4 mmol) and tributyltin hydride (3.89 mL, 14.9 mmol, 97% purity) was added 2,2'-azobisisobutyronitrile (99.4 mg) and the reaction mixture was slowly warmed to 65° C. After stirring for 8 h at 65° C., the cooled reaction mixture was purified by flash chromatography, eluting with a mixture of hexane and EtOAc (50:1) to give 3-(tributylstannyl)-2-propenoic acid phenylmethyl ester (4.80 g, 10.65 mmol) as a mixture of E and Z isomers, in 69% yield. the cooled reaction mixture was purified by flash chromatography eluting with a mixture of hexane and EtOAc (50:1)

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirring mixture of 2-propynoic acid phenylmethyl ester (2.46 g, 15.4 mmol) and tributyltin hydride (3.89 mL, 14.9 mmol, 97% purity) was added 2,2'-azobisisobutyronitrile (99.4 mg) and the reaction mixture was slowly warmed to 65° C. After stirring for 8 h at 65° C., the cooled reaction mixture was purified by flash chromatography, eluting with a mixture of hexane and EtOAc (50:1) to give 3-(tributylstannyl)-2-propenoic acid phenylmethyl ester (4.80 g, 10.65 mmol) as a mixture of E and Z isomers, in 69% yield. the cooled reaction mixture was purified by flash chromatography eluting with a mixture of hexane and EtOAc (50:1)