diphenyl(propyl)phosphane

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

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of triflate 20-3 (0.798 g, 3.0 mmol), Pd(OAc)2 (13.5 mg, 0.060 mmol), and diphenylphosphinopropane (24 mg, 0.060 mmol) in DMF (15 mL) was heated to 70° C. with a gentle flow of CO (g) passing through it. Triethylamine (1.66 mL, 12 mmol) was added followed by trioctylsilane (2.70 mL, 6.0 mmol). The solution was maintained at 70° C. for 2 h, and cooled to room temperature. The solution was diluted with water (10 mL). The mixture was extracted with Et2O (2×30 mL). The combined organic extracts were washed with brine (10 mL), dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (5% acetone/hexanes) to give the desired aldehyde 20-4. cooled to room temperature The mixture was extracted with Et2O (2×30 mL) The combined organic extracts were washed with brine (10 mL) dried over MgSO4 filtered concentrated The residue was purified by flash chromatography (5% acetone/hexanes)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of triflate 20-3 (0.798 g, 3.0 mmol), Pd(OAc)2 (13.5 mg, 0.060 mmol), and diphenylphosphinopropane (24 mg, 0.060 mmol) in DMF (15 mL) was heated to 70° C. with a gentle flow of CO (g) passing through it. Triethylamine (1.66 mL, 12 mmol) was added followed by trioctylsilane (2.70 mL, 6.0 mmol). The solution was maintained at 70° C. for 2 h, and cooled to room temperature. The solution was diluted with water (10 mL). The mixture was extracted with Et2O (2×30 mL). The combined organic extracts were washed with brine (10 mL), dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (5% acetone/hexanes) to give the desired aldehyde 20-4. cooled to room temperature The mixture was extracted with Et2O (2×30 mL) The combined organic extracts were washed with brine (10 mL) dried over MgSO4 filtered concentrated The residue was purified by flash chromatography (5% acetone/hexanes)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of triflate 20-3 (0.798 g, 3.0 mmol), Pd(OAc)2 (13.5 mg, 0.060 mmol), and diphenylphosphinopropane (24 mg, 0.060 mmol) in DMF (15 mL) was heated to 70° C. with a gentle flow of CO (g) passing through it. Triethylamine (1.66 mL, 12 mmol) was added followed by trioctylsilane (2.70 mL, 6.0 mmol). The solution was maintained at 70° C. for 2 h, and cooled to room temperature. The solution was diluted with water (10 mL). The mixture was extracted with Et2O (2×30 mL). The combined organic extracts were washed with brine (10 mL), dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (5% acetone/hexanes) to give the desired aldehyde 20-4. cooled to room temperature The mixture was extracted with Et2O (2×30 mL) The combined organic extracts were washed with brine (10 mL) dried over MgSO4 filtered concentrated The residue was purified by flash chromatography (5% acetone/hexanes)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of triflate 20-3 (0.798 g, 3.0 mmol), Pd(OAc)2 (13.5 mg, 0.060 mmol), and diphenylphosphinopropane (24 mg, 0.060 mmol) in DMF (15 mL) was heated to 70° C. with a gentle flow of CO (g) passing through it. Triethylamine (1.66 mL, 12 mmol) was added followed by trioctylsilane (2.70 mL, 6.0 mmol). The solution was maintained at 70° C. for 2 h, and cooled to room temperature. The solution was diluted with water (10 mL). The mixture was extracted with Et2O (2×30 mL). The combined organic extracts were washed with brine (10 mL), dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (5% acetone/hexanes) to give the desired aldehyde 20-4. cooled to room temperature The mixture was extracted with Et2O (2×30 mL) The combined organic extracts were washed with brine (10 mL) dried over MgSO4 filtered concentrated The residue was purified by flash chromatography (5% acetone/hexanes)

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

Procedure: A solution of the product of Example 6 (780 mg, 1.06 mmol), palladium(II) acetate (42 mg, 0.19 mmol), 1,2-bis(diphenylphosphinopropane (149 mg, 0.36 mmol), formic acid (0.6 mL), and triethylamine (3.0 mL) in anhydrous dimethylformamide (40 mL) was stirred at ambient temperature for 4 d. After concentration, the residue was subjected chromatography (silica gel, 1:1 hexane:ethylacetate, 2-10% methanol, 0.1% ammonium hydroxide). Product containing fractions were concentrated, partitioned between methylene chloride (100 mL) and saturated sodium bicarbonate (100 mL), and the aqueous layer extracted with methylene chloride (50 mL). The combined organic extracts were dried (sodium sulfate), concentrated, and the residue purified by chromatography (silica gel, 1:1 hexane:ethylacetate, 2-10% methanol, 0.1% ammonium hydroxide) to give 267 mg (57%) of the title compound as an oil which gave a white, crystalline solid, mp 107° C., upon trituration with ether/hexane: 1H NMR (300 MHz, CDCl3) d 7.86 (d, J=7.4 Hz, 1H), 7.40 (m, 1H), 7.1-7.3 (m, 6H), 6.97 (t, J=7.3 Hz, 1H), 6.89 (d, J=8.1 Hz, 1H), 6.84 (d, J=8.6 Hz, 2H), 6.66 (s, 1H), 4.07 (t, J=6.1 Hz, 2H), 2.75 (t, J=6.1 Hz, 2H), 2.49 (m, 4H), 1.5-1.7 (m, 4H), 1.4-1.5 (m, 2H); 13C NMR (125 MHz, CDCl3) d 159.1, 151.6, 139.3, 137.1, 133.0, 131.5, 129.8, 129.1, 126.8, 124.6, 124.4, 123.7, 122.6, 121.5, 121.5, 119.3, 116.9, 114.6, 77.6, 65.7, 57.7, 54.9, 25.8, 24.0; MS (FD+) m/e 441 (M+); Anal. calc'd for C28H27NO2 S: C, 76.15; H, 6.17; N, 3.17. Found: C, 75.93; H, 6.44; N, 3.01. After concentration Product containing fractions were concentrated partitioned between methylene chloride (100 mL) and saturated sodium bicarbonate (100 mL) the aqueous layer extracted with methylene chloride (50 mL) The combined organic extracts were dried (sodium sulfate) concentrated the residue purified by chromatography (silica gel, 1:1 hexane:ethylacetate, 2-10% methanol, 0.1% ammonium hydroxide)

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

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

Procedure: A solution of the product of Example 6 (780 mg, 1.06 mmol), palladium(II) acetate (42 mg, 0.19 mmol), 1,2-bis(diphenylphosphinopropane (149 mg, 0.36 mmol), formic acid (0.6 mL), and triethylamine (3.0 mL) in anhydrous dimethylformamide (40 mL) was stirred at ambient temperature for 4 d. After concentration, the residue was subjected chromatography (silica gel, 1:1 hexane:ethylacetate, 2-10% methanol, 0.1% ammonium hydroxide). Product containing fractions were concentrated, partitioned between methylene chloride (100 mL) and saturated sodium bicarbonate (100 mL), and the aqueous layer extracted with methylene chloride (50 mL). The combined organic extracts were dried (sodium sulfate), concentrated, and the residue purified by chromatography (silica gel, 1:1 hexane:ethylacetate, 2-10% methanol, 0.1% ammonium hydroxide) to give 267 mg (57%) of the title compound as an oil which gave a white, crystalline solid, mp 107° C., upon trituration with ether/hexane: 1H NMR (300 MHz, CDCl3) d 7.86 (d, J=7.4 Hz, 1H), 7.40 (m, 1H), 7.1-7.3 (m, 6H), 6.97 (t, J=7.3 Hz, 1H), 6.89 (d, J=8.1 Hz, 1H), 6.84 (d, J=8.6 Hz, 2H), 6.66 (s, 1H), 4.07 (t, J=6.1 Hz, 2H), 2.75 (t, J=6.1 Hz, 2H), 2.49 (m, 4H), 1.5-1.7 (m, 4H), 1.4-1.5 (m, 2H); 13C NMR (125 MHz, CDCl3) d 159.1, 151.6, 139.3, 137.1, 133.0, 131.5, 129.8, 129.1, 126.8, 124.6, 124.4, 123.7, 122.6, 121.5, 121.5, 119.3, 116.9, 114.6, 77.6, 65.7, 57.7, 54.9, 25.8, 24.0; MS (FD+) m/e 441 (M+); Anal. calc'd for C28H27NO2 S: C, 76.15; H, 6.17; N, 3.17. Found: C, 75.93; H, 6.44; N, 3.01. After concentration Product containing fractions were concentrated partitioned between methylene chloride (100 mL) and saturated sodium bicarbonate (100 mL) the aqueous layer extracted with methylene chloride (50 mL) The combined organic extracts were dried (sodium sulfate) concentrated the residue purified by chromatography (silica gel, 1:1 hexane:ethylacetate, 2-10% methanol, 0.1% ammonium hydroxide)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of triflate 20-3 (0.798 g, 3.0 mmol), Pd(OAc)2 (13.5 mg, 0.060 mmol), and diphenylphosphinopropane (24 mg, 0.060 mmol) in DMF (15 mL) was heated to 70° C. with a gentle flow of CO (g) passing through it. Triethylamine (1.66 mL, 12 mmol) was added followed by trioctylsilane (2.70 mL, 6.0 mmol). The solution was maintained at 70° C. for 2 h, and cooled to room temperature. The solution was diluted with water (10 mL). The mixture was extracted with Et2O (2×30 mL). The combined organic extracts were washed with brine (10 mL), dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (5% acetone/hexanes) to give the desired aldehyde 20-4. cooled to room temperature The mixture was extracted with Et2O (2×30 mL) The combined organic extracts were washed with brine (10 mL) dried over MgSO4 filtered concentrated The residue was purified by flash chromatography (5% acetone/hexanes)

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

Procedure: An autoclave is initially charged under argon with 58 ml of N,N-dimethylformamide, 42 ml of methanol, 0.347 g of diphenylphosphinopropane and 0.189 g of palladium(II) acetate. The reaction mixture is stirred at room temperature over 20 minutes. Subsequently, 7.73 g of tert-butyl 3-hydroxy-4-(4-trifluoromethanesulphonyloxyphenyl)piperidine-1-carboxylate and 3.75 g of triethylamine are added and the autoclave is charged with 5 bar of carbon monoxide. The reaction mixture is subsequently stirred at 700 and 5 bar of pressure over 3 hours. Subsequently, the reaction mixture is cooled and a solution of palladium(II) acetate (0.095 g) and diphenylphosphinopropane (0.175 g) in 29 ml of N,N-dimethylformamide and 21 ml of methanol is added. The reaction mixture is subsequently stirred at 70° and 5 bar of carbon monoxide for a further 3 hours. The reaction solution is cooled and stirred with 200 ml of water and 250 ml of tert-butyl methyl ether. The phases are separated and the aqueous phase is extracted once more with 250 ml of tert-butyl methyl ether. The organic phases are combined and concentrated by evaporation to dryness. The title compound is obtained as a colourless solid from the residue by means of flash chromatography (SiO2 60F). Rf=0.20 (1:1 EtOAc-heptane); Rt=4.15. The reaction mixture is subsequently stirred at 700 and 5 bar of pressure over 3 hours Subsequently, the reaction mixture is cooled The reaction mixture is subsequently stirred at 70° The reaction solution is cooled The phases are separated the aqueous phase is extracted once more with 250 ml of tert-butyl methyl ether concentrated by evaporation to dryness

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

Procedure: After adding a solution of 4-acetyloxy-3,5-dimethyl-6-(6-(trifluoromethanesulfonyloxy)benzofuran-2-yl)-2H-pyran-2-one (350 mg) in THF (5 ml) and Et3N (80 mg) to a mixed solution of palladium acetate (3.5 mg) and diphenylphospinopropane (6.5 mg) in DMSO (5 ml) and MeOH (5 ml), the mixture was stirred at room temperature for one hour under a carbon monoxide atmosphere, and then further stirred at 80° C. for 2 hours. The reaction solution was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (n-hexane/AcOEt=1/1) to obtain 4-acetyloxy-3,5-dimethyl-6-(6-(methoxycarbonyl) benzofuran-2-yl)-2H-pyran-2-one. further stirred at 80° C. for 2 hours The reaction solution was concentrated under reduced pressure the residue was purified by silica gel column chromatography (n-hexane/AcOEt=1/1)

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

Procedure: A solution of the product of Example 6 (780 mg, 1.06 mmol), palladium(II) acetate (42 mg, 0.19 mmol), 1,2-bis(diphenylphosphinopropane (149 mg, 0.36 mmol), formic acid (0.6 mL), and triethylamine (3.0 mL) in anhydrous dimethylformamide (40 mL) was stirred at ambient temperature for 4 d. After concentration, the residue was subjected chromatography (silica gel, 1:1 hexane:ethylacetate, 2-10% methanol, 0.1% ammonium hydroxide). Product containing fractions were concentrated, partitioned between methylene chloride (100 mL) and saturated sodium bicarbonate (100 mL), and the aqueous layer extracted with methylene chloride (50 mL). The combined organic extracts were dried (sodium sulfate), concentrated, and the residue purified by chromatography (silica gel, 1:1 hexane:ethylacetate, 2-10% methanol, 0.1% ammonium hydroxide) to give 267 mg (57%) of the title compound as an oil which gave a white, crystalline solid, mp 107° C., upon trituration with ether/hexane: 1H NMR (300 MHz, CDCl3) d 7.86 (d, J=7.4 Hz, 1H), 7.40 (m, 1H), 7.1-7.3 (m, 6H), 6.97 (t, J=7.3 Hz, 1H), 6.89 (d, J=8.1 Hz, 1H), 6.84 (d, J=8.6 Hz, 2H), 6.66 (s, 1H), 4.07 (t, J=6.1 Hz, 2H), 2.75 (t, J=6.1 Hz, 2H), 2.49 (m, 4H), 1.5-1.7 (m, 4H), 1.4-1.5 (m, 2H); 13C NMR (125 MHz, CDCl3) d 159.1, 151.6, 139.3, 137.1, 133.0, 131.5, 129.8, 129.1, 126.8, 124.6, 124.4, 123.7, 122.6, 121.5, 121.5, 119.3, 116.9, 114.6, 77.6, 65.7, 57.7, 54.9, 25.8, 24.0; MS (FD+) m/e 441 (M+); Anal. calc'd for C28H27NO2 S: C, 76.15; H, 6.17; N, 3.17. Found: C, 75.93; H, 6.44; N, 3.01. After concentration Product containing fractions were concentrated partitioned between methylene chloride (100 mL) and saturated sodium bicarbonate (100 mL) the aqueous layer extracted with methylene chloride (50 mL) The combined organic extracts were dried (sodium sulfate) concentrated the residue purified by chromatography (silica gel, 1:1 hexane:ethylacetate, 2-10% methanol, 0.1% ammonium hydroxide)