7-bromobicyclo[2.2.1]heptane

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

Procedure: Lithium metal (78 mg, 11.2 mmol) was scraped under a tetrahydrofuran solution to remove the coating and then added to a solution of 4,4′-tertbutyl biphenyl (2.67 g, 10.02 mmol) in tetrahydrofuran (15 mL) under argon. The mixture was cooled to 0° C. and a blue-green color appeared over time. After 3 h, all the lithium metal was dissolved and the mixture was cannulated into a −78° C. mixture of 7-bromo-bicyclo[2.2.1]heptane (1.0 g, 5.71 mmol) in tetrahydrofuran (5 mL). The mixture turned colorless and then developed a red color and stirred at −78° C. for 30 min. The mixture was then quickly poured over freshly crushed dry ice. The resulting yellow mixture was allowed to warm to 25° C. and concentrated in vacuo. The residue was dissolved in diethyl ether (30 mL) and extracted with a 1N aqueous sodium hydroxide solution (2×15 mL). The combined aqueous extracts were acidified with concentrated hydrochloric acid and extracted with diethyl ether (3×10 mL). The combined organic layers were washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated in vacuo to afford bicyclo[2.2.1]hept-7-yl-acetic acid (554 mg, 63%) to remove the coating was cannulated into a −78° C. to warm to 25° C. concentrated in vacuo The residue was dissolved in diethyl ether (30 mL) extracted with a 1N aqueous sodium hydroxide solution (2×15 mL) extracted with diethyl ether (3×10 mL) The combined organic layers were washed with a saturated aqueous solution of sodium chloride dried over magnesium sulfate filtered concentrated in vacuo

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 4-4′-di-t-butylbiphenyl (8.25 g, 31 mmol) in anhydrous tetrahydrofuran (70 mL) under a nitrogen atmosphere was added freshly cleaned lithium wire (0.21 g, 30 mmol). The resulting mixture was stirred at room temperature for 15 minutes to initiate reaction, then cooled in an ice bath and stirred for an additional 4 hours. The resulting blue solution was cooled with a dry ice/acetone bath and a solution of 7-bromo-bicyclo[2.2.1]heptane (2.0 g, 11.4 mmol) in anhydrous tetrahydrofuran (5 mL) was added in one portion. The reaction mixture was stirred for 20 minutes, during which time the blue color changed to orange. Solid dry ice was then added to the reaction, which became colorless. The dry ice bath/acetone bath was removed and the reaction was stirred for 2 hours, during which time it came up to room temperature. 2.5 N aqueous sodium hydroxide (200 mL) was added and the mixture was stirred for 5 minutes. The layers were separated and the aqueous layer was extracted twice with diethyl ether (50 mL). The aqueous layer was then made acidic by addition of concentrated HCl and extracted with three portions of diethyl ether (75 mL). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated to yield the desired compound of formula (VIII) as a white solid (1.54 g, 96%), mp=74–75 ° C. (lit. mp=77.5–785° C., J. Am. Chem. Soc. 1954, 76, 4072). reaction cooled in an ice bath stirred for an additional 4 hours The resulting blue solution was cooled with a dry ice/acetone bath The reaction mixture was stirred for 20 minutes, during which time the blue color The dry ice bath/acetone bath was removed the reaction was stirred for 2 hours, during which time it came up to room temperature 2.5 N aqueous sodium hydroxide (200 mL) was added the mixture was stirred for 5 minutes The layers were separated the aqueous layer was extracted twice with diethyl ether (50 mL) made acidic by addition of concentrated HCl extracted with three portions of diethyl ether (75 mL) The combined organic layers were dried over anhydrous magnesium sulfate concentrated

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

Procedure: To a solution of 4-4′-di-t-butylbiphenyl (8.25 g, 31 mmol) in anhydrous tetrahydrofuran (70 mL) under a nitrogen atmosphere was added freshly cleaned lithium wire (0.21 g, 30 mmol). The resulting mixture was stirred at room temperature for 15 minutes to initiate reaction, then cooled in an ice bath and stirred for an additional 4 hours. The resulting blue solution was cooled with a dry ice/acetone bath and a solution of 7-bromo-bicyclo[2.2.1]heptane (2.0 g, 11.4 mmol) in anhydrous tetrahydrofuran (5 mL) was added in one portion. The reaction mixture was stirred for 20 minutes, during which time the blue color changed to orange. Solid dry ice was then added to the reaction, which became colorless. The dry ice bath/acetone bath was removed and the reaction was stirred for 2 hours, during which time it came up to room temperature. 2.5 N aqueous sodium hydroxide (200 mL) was added and the mixture was stirred for 5 minutes. The layers were separated and the aqueous layer was extracted twice with diethyl ether (50 mL). The aqueous layer was then made acidic by addition of concentrated HCl and extracted with three portions of diethyl ether (75 mL). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated to yield the desired compound of formula (VIII) as a white solid (1.54 g, 96%), mp=74–75 ° C. (lit. mp=77.5–785° C., J. Am. Chem. Soc. 1954, 76, 4072). reaction cooled in an ice bath stirred for an additional 4 hours The resulting blue solution was cooled with a dry ice/acetone bath The reaction mixture was stirred for 20 minutes, during which time the blue color The dry ice bath/acetone bath was removed the reaction was stirred for 2 hours, during which time it came up to room temperature 2.5 N aqueous sodium hydroxide (200 mL) was added the mixture was stirred for 5 minutes The layers were separated the aqueous layer was extracted twice with diethyl ether (50 mL) made acidic by addition of concentrated HCl extracted with three portions of diethyl ether (75 mL) The combined organic layers were dried over anhydrous magnesium sulfate concentrated

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

Procedure: Lithium metal (78 mg, 11.2 mmol) was scraped under a tetrahydrofuran solution to remove the coating and then added to a solution of 4,4′-tertbutyl biphenyl (2.67 g, 10.02 mmol) in tetrahydrofuran (15 mL) under argon. The mixture was cooled to 0° C. and a blue-green color appeared over time. After 3 h, all the lithium metal was dissolved and the mixture was cannulated into a −78° C. mixture of 7-bromo-bicyclo[2.2.1]heptane (1.0 g, 5.71 mmol) in tetrahydrofuran (5 mL). The mixture turned colorless and then developed a red color and stirred at −78° C. for 30 min. The mixture was then quickly poured over freshly crushed dry ice. The resulting yellow mixture was allowed to warm to 25° C. and concentrated in vacuo. The residue was dissolved in diethyl ether (30 mL) and extracted with a 1N aqueous sodium hydroxide solution (2×15 mL). The combined aqueous extracts were acidified with concentrated hydrochloric acid and extracted with diethyl ether (3×10 mL). The combined organic layers were washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated in vacuo to afford bicyclo[2.2.1]hept-7-yl-acetic acid (554 mg, 63%) to remove the coating was cannulated into a −78° C. to warm to 25° C. concentrated in vacuo The residue was dissolved in diethyl ether (30 mL) extracted with a 1N aqueous sodium hydroxide solution (2×15 mL) extracted with diethyl ether (3×10 mL) The combined organic layers were washed with a saturated aqueous solution of sodium chloride dried over magnesium sulfate filtered concentrated in vacuo

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

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

Procedure: Lithium metal (78 mg, 11.2 mmol) was scraped under a tetrahydrofuran solution to remove the coating and then added to a solution of 4,4′-tertbutyl biphenyl (2.67 g, 10.02 mmol) in tetrahydrofuran (15 mL) under argon. The mixture was cooled to 0° C. and a blue-green color appeared over time. After 3 h, all the lithium metal was dissolved and the mixture was cannulated into a −78° C. mixture of 7-bromo-bicyclo[2.2.1]heptane (1.0 g, 5.71 mmol) in tetrahydrofuran (5 mL). The mixture turned colorless and then developed a red color and stirred at −78° C. for 30 min. The mixture was then quickly poured over freshly crushed dry ice. The resulting yellow mixture was allowed to warm to 25° C. and concentrated in vacuo. The residue was dissolved in diethyl ether (30 mL) and extracted with a 1N aqueous sodium hydroxide solution (2×15 mL). The combined aqueous extracts were acidified with concentrated hydrochloric acid and extracted with diethyl ether (3×10 mL). The combined organic layers were washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated in vacuo to afford bicyclo[2.2.1]hept-7-yl-acetic acid (554 mg, 63%) to remove the coating was cannulated into a −78° C. to warm to 25° C. concentrated in vacuo The residue was dissolved in diethyl ether (30 mL) extracted with a 1N aqueous sodium hydroxide solution (2×15 mL) extracted with diethyl ether (3×10 mL) The combined organic layers were washed with a saturated aqueous solution of sodium chloride dried over magnesium sulfate filtered concentrated in vacuo

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 15.9 g (81 mmol) of 7-Bromo-bicyclo[2.2.1]heptane were added dropwise to 2 g magnesium (81 mmol) in 25 ml of diethyl ether and refluxed for 2.5 h. The mixture was cooled to 0-5° C. and 6.3 ml (81 mmol) of DMF were added dropwise. The mixture was then refluxed for 2 h, cooled to room temperature and the white solid filtered off and washed with ether. The filtrate was reduced and 4.87 g of a white solid were obtained. The intermediate was used without further characterization. refluxed for 2.5 h The mixture was then refluxed for 2 h cooled to room temperature the white solid filtered off washed with ether

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

Procedure: To a solution of 4-4′-di-t-butylbiphenyl (8.25 g, 31 mmol) in anhydrous tetrahydrofuran (70 mL) under a nitrogen atmosphere was added freshly cleaned lithium wire (0.21 g, 30 mmol). The resulting mixture was stirred at room temperature for 15 minutes to initiate reaction, then cooled in an ice bath and stirred for an additional 4 hours. The resulting blue solution was cooled with a dry ice/acetone bath and a solution of 7-bromo-bicyclo[2.2.1]heptane (2.0 g, 11.4 mmol) in anhydrous tetrahydrofuran (5 mL) was added in one portion. The reaction mixture was stirred for 20 minutes, during which time the blue color changed to orange. Solid dry ice was then added to the reaction, which became colorless. The dry ice bath/acetone bath was removed and the reaction was stirred for 2 hours, during which time it came up to room temperature. 2.5 N aqueous sodium hydroxide (200 mL) was added and the mixture was stirred for 5 minutes. The layers were separated and the aqueous layer was extracted twice with diethyl ether (50 mL). The aqueous layer was then made acidic by addition of concentrated HCl and extracted with three portions of diethyl ether (75 mL). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated to yield the desired compound of formula (VIII) as a white solid (1.54 g, 96%), mp=74–75 ° C. (lit. mp=77.5–785° C., J. Am. Chem. Soc. 1954, 76, 4072). reaction cooled in an ice bath stirred for an additional 4 hours The resulting blue solution was cooled with a dry ice/acetone bath The reaction mixture was stirred for 20 minutes, during which time the blue color The dry ice bath/acetone bath was removed the reaction was stirred for 2 hours, during which time it came up to room temperature 2.5 N aqueous sodium hydroxide (200 mL) was added the mixture was stirred for 5 minutes The layers were separated the aqueous layer was extracted twice with diethyl ether (50 mL) made acidic by addition of concentrated HCl extracted with three portions of diethyl ether (75 mL) The combined organic layers were dried over anhydrous magnesium sulfate concentrated