5-(2,3-difluorophenyl)cycloheptene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: See: D. A. Spiegel et al. Tetrahedron 2002, 58, 6545-6554. In a 250 mL round-bottomed flask (t=g) was added (Z)-5-(2,3-difluorophenyl)cyclohept-1-ene (1.249 g, 6.00 mmol) and NMO (1.546 g, 13.19 mmol) in Acetone (9 mL) and Water (0.18 mL) to give a white suspension. Osmium tetroxide (0.301 mL, 0.024 mmol) (2.5 wt % solution in 2-methyl-2-propanol) was added. The mixture was stirred at room temperature. NMO gradually dissolved within 30 minutes to become a yellow solution. 1 h: TLC showed complete conversion to a much polar spot. Sodium bisulfite (200 mg) was added and stirring continued for 30 minutes. Acetone was stripped off and the residue was extracted with EtOAc three times. The combined organic layers were washed with brine, dried and concentrated to a white solid (crude weight: 1.7 g). It was directly carried onto next reaction. to give a white suspension 1 h stirring the residue was extracted with EtOAc three times The combined organic layers were washed with brine dried concentrated to a white solid (crude weight It was directly carried onto next reaction

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 250 mL round-bottomed flask (t=g) was added (Z)-1-(2,3-difluorophenyl)cyclohept-4-enol (2.05 g, 9.14 mmol) in CH2Cl2 (40 mL) to give a colorless solution. Triethylsilane (7.30 mL, 45.7 mmol) was added, followed by TFA (20 mL). The mixture was stirred at room temperature for 3 hours: TLC showed a complete conversion (Rf=0.42 by pure hexane). It was concentrated down to a bi-layer oil (the lower layer wasn't hexane-soluble). Purification by FCC using only hexane afforded the desired product as a colorless oil (1.684 g, 88%). 1H NMR (400 MHz, CDCl3) δ 7.00-6.90 (m, 3H), 5.90-5.82 (m, 2H), 3.20-3.05 (m, 1H), 2.40-2.15 (m, 4H), 1.90-1.78 (m, 2H), 1.60-1.40 (m, 2H). to give a colorless solution It was concentrated down to a bi-layer oil (the lower layer wasn't hexane-soluble) Purification by FCC

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 250 mL round-bottomed flask (t=g) was added (Z)-1-(2,3-difluorophenyl)cyclohept-4-enol (2.05 g, 9.14 mmol) in CH2Cl2 (40 mL) to give a colorless solution. Triethylsilane (7.30 mL, 45.7 mmol) was added, followed by TFA (20 mL). The mixture was stirred at room temperature for 3 hours: TLC showed a complete conversion (Rf=0.42 by pure hexane). It was concentrated down to a bi-layer oil (the lower layer wasn't hexane-soluble). Purification by FCC using only hexane afforded the desired product as a colorless oil (1.684 g, 88%). 1H NMR (400 MHz, CDCl3) δ 7.00-6.90 (m, 3H), 5.90-5.82 (m, 2H), 3.20-3.05 (m, 1H), 2.40-2.15 (m, 4H), 1.90-1.78 (m, 2H), 1.60-1.40 (m, 2H). to give a colorless solution It was concentrated down to a bi-layer oil (the lower layer wasn't hexane-soluble) Purification by FCC

反応条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ref. Plietker, B. J. Org. Chem. 2004, 69, 8287-8296. In a 500 mL round-bottomed flask (t=g) was added sodium bicarbonate (827 mg, 9.84 mmol) with a stirring bar. Ruthenium(III) chloride (8.17 mg, 0.039 mmol) was added (aqueous solution was used in the ref but it was difficult to completely dissolve). To the solids was added water (3.94 mL), EtOAc (20 ml), and MeCN (20 ml) to afford a brown suspension. Oxone (1.21E+04 mg, 19.69 mmol) was added in one portion, resulting in the formation of a bright yellow suspension. The mixture was cooled to −20° C. (Z)-5-(2,3-difluorophenyl)cyclohept-1-ene (820 mg, 3.94 mmol) was added (with 7.2 ml 1/1 EtOAc/MeCN wash). The color instantly turned to slightly tan. The reaction was stirred at −20 ˜−15° C. for 1.5 hours. TLC showed no reaction. Warmed up to 0° C. for 10 minutes, but by TLC the reaction didn't improve much. It was warmed up to room temperature for 15-20 minutes. TLC showed disappearing of one major less polar spot (a minor one remained) and appearance of a more polar, slightly uv-active spot. The solids were filtered and washed with EtOAc. The organic solution was washed with aqueous NaHSO3 solution. The organic layer was dried with Na2SO4 and concentrated to a colorless oil. It was purified by FCC up to 5% MeOH/CH2Cl2. The more polar peak/peaks were pooled and concentrated to a colorless oil (169 mg, 18%). It was directly carried onto the next protection reaction. to completely dissolve) to afford a brown suspension resulting in the formation of a bright yellow suspension was added (with 7.2 ml 1/1 EtOAc/MeCN wash) no reaction Warmed up to 0° C. for 10 minutes by TLC the reaction It was warmed up to room temperature for 15-20 minutes The solids were filtered washed with EtOAc The organic solution was washed with aqueous NaHSO3 solution The organic layer was dried with Na2SO4 concentrated to a colorless oil It was purified by FCC up to 5% MeOH/CH2Cl2 concentrated to a colorless oil (169 mg, 18%) It was directly carried onto the next protection reaction

反応条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ref. Plietker, B. J. Org. Chem. 2004, 69, 8287-8296. In a 500 mL round-bottomed flask (t=g) was added sodium bicarbonate (827 mg, 9.84 mmol) with a stirring bar. Ruthenium(III) chloride (8.17 mg, 0.039 mmol) was added (aqueous solution was used in the ref but it was difficult to completely dissolve). To the solids was added water (3.94 mL), EtOAc (20 ml), and MeCN (20 ml) to afford a brown suspension. Oxone (1.21E+04 mg, 19.69 mmol) was added in one portion, resulting in the formation of a bright yellow suspension. The mixture was cooled to −20° C. (Z)-5-(2,3-difluorophenyl)cyclohept-1-ene (820 mg, 3.94 mmol) was added (with 7.2 ml 1/1 EtOAc/MeCN wash). The color instantly turned to slightly tan. The reaction was stirred at −20 ˜−15° C. for 1.5 hours. TLC showed no reaction. Warmed up to 0° C. for 10 minutes, but by TLC the reaction didn't improve much. It was warmed up to room temperature for 15-20 minutes. TLC showed disappearing of one major less polar spot (a minor one remained) and appearance of a more polar, slightly uv-active spot. The solids were filtered and washed with EtOAc. The organic solution was washed with aqueous NaHSO3 solution. The organic layer was dried with Na2SO4 and concentrated to a colorless oil. It was purified by FCC up to 5% MeOH/CH2Cl2. The more polar peak/peaks were pooled and concentrated to a colorless oil (169 mg, 18%). It was directly carried onto the next protection reaction. to completely dissolve) to afford a brown suspension resulting in the formation of a bright yellow suspension was added (with 7.2 ml 1/1 EtOAc/MeCN wash) no reaction Warmed up to 0° C. for 10 minutes by TLC the reaction It was warmed up to room temperature for 15-20 minutes The solids were filtered washed with EtOAc The organic solution was washed with aqueous NaHSO3 solution The organic layer was dried with Na2SO4 concentrated to a colorless oil It was purified by FCC up to 5% MeOH/CH2Cl2 concentrated to a colorless oil (169 mg, 18%) It was directly carried onto the next protection reaction

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 100 mL round-bottomed flask (t=g) was added (Z)-1-(2,3-difluorophenyl)cyclohept-4-enol (872 mg, 3.89 mmol) in CH2Cl2 (16 mL) to give a colorless solution. Triethylsilane (3.11 mL, 19.44 mmol) was added, following by TFA (8.00 mL). The mixture was stirred at room temperature for 2.5 hours. TLC showed clean conversion to a less polar compound. It was concentrated down and purification by FCC up to 20% Et2O in hexane afforded the desired product as a colorless oil (769 mg, 95%). The product was quickly eluted out. 1H NMR (the major peaks are the same as these in the later synthesis) confirmed the structure. to give a colorless solution It was concentrated down and purification by FCC up to 20% Et2O in hexane

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: See: D. A. Spiegel et al. Tetrahedron 2002, 58, 6545-6554. In a 250 mL round-bottomed flask (t=g) was added (Z)-5-(2,3-difluorophenyl)cyclohept-1-ene (1.249 g, 6.00 mmol) and NMO (1.546 g, 13.19 mmol) in Acetone (9 mL) and Water (0.18 mL) to give a white suspension. Osmium tetroxide (0.301 mL, 0.024 mmol) (2.5 wt % solution in 2-methyl-2-propanol) was added. The mixture was stirred at room temperature. NMO gradually dissolved within 30 minutes to become a yellow solution. 1 h: TLC showed complete conversion to a much polar spot. Sodium bisulfite (200 mg) was added and stirring continued for 30 minutes. Acetone was stripped off and the residue was extracted with EtOAc three times. The combined organic layers were washed with brine, dried and concentrated to a white solid (crude weight: 1.7 g). It was directly carried onto next reaction. to give a white suspension 1 h stirring the residue was extracted with EtOAc three times The combined organic layers were washed with brine dried concentrated to a white solid (crude weight It was directly carried onto next reaction

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 250 mL round-bottomed flask (t=g) was added (Z)-1-(2,3-difluorophenyl)cyclohept-4-enol (2.05 g, 9.14 mmol) in CH2Cl2 (40 mL) to give a colorless solution. Triethylsilane (7.30 mL, 45.7 mmol) was added, followed by TFA (20 mL). The mixture was stirred at room temperature for 3 hours: TLC showed a complete conversion (Rf=0.42 by pure hexane). It was concentrated down to a bi-layer oil (the lower layer wasn't hexane-soluble). Purification by FCC using only hexane afforded the desired product as a colorless oil (1.684 g, 88%). 1H NMR (400 MHz, CDCl3) δ 7.00-6.90 (m, 3H), 5.90-5.82 (m, 2H), 3.20-3.05 (m, 1H), 2.40-2.15 (m, 4H), 1.90-1.78 (m, 2H), 1.60-1.40 (m, 2H). to give a colorless solution It was concentrated down to a bi-layer oil (the lower layer wasn't hexane-soluble) Purification by FCC

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ref. Plietker, B. J. Org. Chem. 2004, 69, 8287-8296. In a 500 mL round-bottomed flask (t=g) was added sodium bicarbonate (827 mg, 9.84 mmol) with a stirring bar. Ruthenium(III) chloride (8.17 mg, 0.039 mmol) was added (aqueous solution was used in the ref. but it was difficult to completely dissolve). To the solids was added water (3.94 mL), EtOAc (20 ml), and MeCN (20 ml) to afford a brown suspension. Oxone (1.21E+04 mg, 19.69 mmol) was added in one portion, resulting in the formation of a bright yellow suspension. The mixture was cooled to −20° C. (Z)-5-(2,3-difluorophenyl)cyclohept-1-ene (820 mg, 3.94 mmol) was added (with 7.2 ml 1/l EtOAc/MeCN wash). The color instantly turned to slightly tan. The reaction was stirred at −20˜−15° C. for 1.5 hours. TLC showed no reaction. Warmed up to 0° C. for 10 minutes, but by TLC the reaction didn't improve much. It was warmed up to room temperature for 15-20 minutes. TLC showed disappearing of one major less polar spot (a minor one remained) and appearance of a more polar, slightly uv-active spot. The solids were filtered and washed with EtOAc. The organic solution was washed with aqueous NaHSO3 solution. The organic layer was dried with Na2SO4 and concentrated to a colorless oil. It was purified by FCC up to 5% MeOH/CH2Cl2. The more polar peak/peaks were pooled and concentrated to a colorless oil (169 mg, 18%). It was directly carried onto the next protection reaction. to completely dissolve) to afford a brown suspension resulting in the formation of a bright yellow suspension was added (with 7.2 ml 1/l EtOAc/MeCN wash) no reaction by TLC the reaction It was warmed up to room temperature for 15-20 minutes The solids were filtered washed with EtOAc The organic solution was washed with aqueous NaHSO3 solution The organic layer was dried with Na2SO4 concentrated to a colorless oil It was purified by FCC up to 5% MeOH/CH2Cl2 concentrated to a colorless oil (169 mg, 18%) It was directly carried onto the next protection reaction

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 100 mL round-bottomed flask (t=g) was added (Z)-1-(2,3-difluorophenyl)cyclohept-4-enol (872 mg, 3.89 mmol) in CH2Cl2 (16 mL) to give a colorless solution. Triethylsilane (3.11 mL, 19.44 mmol) was added, following by TFA (8.00 mL). The mixture was stirred at room temperature for 2.5 hours. TLC showed clean conversion to a less polar compound. It was concentrated down and purification by FCC up to 20% Et2O in hexane afforded the desired product as a colorless oil (769 mg, 95%). The product was quickly eluted out. 1H NMR (the major peaks are the same as these in the later synthesis) confirmed the structure. to give a colorless solution It was concentrated down and purification by FCC up to 20% Et2O in hexane