4-(bromomethyl)-1,2-diethylbenzene

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

Procedure: 6.7 g (0.29 mol) sodium were added to 300 mL EtOH under an argon atmosphere. 60.0 g (0.27 mol) ethyl acetamidomalonate were added to the resulting solution, stirred for 1.5 h and then 62.0 g (0.27 mol) 4-bromomethyl-1,2-diethyl-benzene were slowly added dropwise. The reaction mixture was stirred overnight at RT, poured onto 1 L of water and vigorously stirred for 1 h at RT. The precipitate formed was suction filtered, suspended twice with a little water, suction filtered and dried. The reaction mixture was stirred overnight at RT vigorously stirred for 1 h at RT The precipitate formed filtered filtered dried

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

Procedure: In a three-necked flask 250 mL of a 1 molar solution of lithium-bis-(trimethylsilyl)-amide (250 mmol) and 15.4 g (64.1 mmol) of (1S,2S)-pseudoephedrine-glycinamide hydrate were added to 500 mL of THF under a nitrogen atmosphere and while cooling with ice. The mixture was stirred for 1.5 h at 0° C., slowly combined with 15.4 g (67.1 mmol) of 4-bromomethyl-1,2-diethyl-benzene, dissolved in 10 mL of THF, and stirred for 2 h at 0° C. While cooling with ice 10 mL of water and 6 mL semiconcentrated HCl were added dropwise, stirred for a further 20 min and made alkaline with concentrated ammonia solution. The reaction mixture was exhaustively extracted with EtOAc, the combined organic phases were dried and evaporated down under reduced pressure. The residue remaining was purified through silica gel. The desired product was obtained in the form of a solid. while cooling with ice stirred for 2 h at 0° C were added dropwise stirred for a further 20 min The reaction mixture was exhaustively extracted with EtOAc the combined organic phases were dried evaporated down under reduced pressure The residue remaining was purified through silica gel

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

Procedure: In a three-necked flask 250 mL of a 1 molar solution of lithium-bis-(trimethylsilyl)-amide (250 mmol) and 15.4 g (64.1 mmol) of (1S,2S)-pseudoephedrine-glycinamide hydrate were added to 500 mL of THF under a nitrogen atmosphere and while cooling with ice. The mixture was stirred for 1.5 h at 0° C., slowly combined with 15.4 g (67.1 mmol) of 4-bromomethyl-1,2-diethyl-benzene, dissolved in 10 mL of THF, and stirred for 2 h at 0° C. While cooling with ice 10 mL of water and 6 mL semiconcentrated HCl were added dropwise, stirred for a further 20 min and made alkaline with concentrated ammonia solution. The reaction mixture was exhaustively extracted with EtOAc, the combined organic phases were dried and evaporated down under reduced pressure. The residue remaining was purified through silica gel. The desired product was obtained in the form of a solid. while cooling with ice stirred for 2 h at 0° C were added dropwise stirred for a further 20 min The reaction mixture was exhaustively extracted with EtOAc the combined organic phases were dried evaporated down under reduced pressure The residue remaining was purified through silica gel

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,2-Diethylbenzene (3.4 g, 23.3 mmol) and paraformaldehyde (2.5 g, 84 mmol) were suspended in glacial acetic acid (60 mL), hydrobromic acid (38% in acetic acid, 8 mL) was added, the reaction flask was sealed with a rubber septum and heated to 80° C. After 4 hours the solution was cooled to ambient temperature and paraformaldehyde (2.5 g, 84 mmol) and hydrobromic acid (38% in acetic acid, 8 mL) were added. The mixture was reheated to 80° C. for 4 hours. Further paraformaldehyde (2.5 g, 84 mmol) and hydrobromic acid (38% in acetic acid, 8 mL) were and the reaction let stir at 80° C. overnight. After a total of 24 hours of reaction time the solution was cooled, diluted with water and diethyl ether, then the layers separated. The organic layers were washed carefully with saturated sodium bicarbonate (4×50 mL), brine, then dried with sodium sulfate, filtered and concentrated in the presence of silica. Purified by column chromatography eluting with 100% hexanes. Concentrated fractions to a yield 4-(bromomethyl)-1,2-diethylbenzene (4.05 g, 77%) 1H NMR (300 MHz, CDCl3) δ 1.21 (m, 6H) 2.64 (m, 4H), 4.47 (s, 2H), 7.1-7.2 (m, 3H). the reaction flask was sealed with a rubber septum After 4 hours the solution was cooled to ambient temperature After a total of 24 hours of reaction time the solution was cooled the layers separated The organic layers were washed carefully with saturated sodium bicarbonate (4×50 mL), brine dried with sodium sulfate filtered concentrated in the presence of silica Purified by column chromatography eluting with 100% hexanes

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

Procedure: Under a nitrogen atmosphere 8.14 g (354 mmol) of sodium was added in batches to 200 mL abs. EtOH and stirred until fully dissolved. 76.9 g (354 mmol) diethyl 2-acetylaminomalonate was then added to this solution, whereupon the sodium salt formed was precipitated. After the addition of 150 mL 1,4-dioxane a solution of 80 g (352 mmol) of 4-bromomethyl-1,2-diethyl-benzene in 500 mL of 1,4-dioxane was added dropwise to this suspension. The reaction solution was kept at 50° C. for 2 hours and then stirred for 16 hours at RT. The solvent was distilled off i. vac., the oily residue was combined with water, while the product was obtained in the form of white crystals. These were suction filtered, washed with water and reacted without any further purification. until fully dissolved formed was precipitated was added dropwise to this suspension The solvent was distilled off i was obtained in the form of white crystals These were suction filtered, washed with water reacted without any further purification

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

Procedure: 6.7 g (0.29 mol) sodium were added to 300 mL EtOH under an argon atmosphere. 60.0 g (0.27 mol) ethyl acetamidomalonate were added to the resulting solution, stirred for 1.5 h and then 62.0 g (0.27 mol) 4-bromomethyl-1,2-diethyl-benzene were slowly added dropwise. The reaction mixture was stirred overnight at RT, poured onto 1 L of water and vigorously stirred for 1 h at RT. The precipitate formed was suction filtered, suspended twice with a little water, suction filtered and dried. The reaction mixture was stirred overnight at RT vigorously stirred for 1 h at RT The precipitate formed filtered filtered dried

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

Procedure: In a three-necked flask 250 mL of a 1 molar solution of lithium-bis-(trimethylsilyl)-amide (250 mmol) and 15.4 g (64.1 mmol) of (1S,2S)-pseudoephedrine-glycinamide hydrate were added to 500 mL of THF under a nitrogen atmosphere and while cooling with ice. The mixture was stirred for 1.5 h at 0° C., slowly combined with 15.4 g (67.1 mmol) of 4-bromomethyl-1,2-diethyl-benzene, dissolved in 10 mL of THF, and stirred for 2 h at 0° C. While cooling with ice 10 mL of water and 6 mL semiconcentrated HCl were added dropwise, stirred for a further 20 min and made alkaline with concentrated ammonia solution. The reaction mixture was exhaustively extracted with EtOAc, the combined organic phases were dried and evaporated down under reduced pressure. The residue remaining was purified through silica gel. The desired product was obtained in the form of a solid. while cooling with ice stirred for 2 h at 0° C were added dropwise stirred for a further 20 min The reaction mixture was exhaustively extracted with EtOAc the combined organic phases were dried evaporated down under reduced pressure The residue remaining was purified through silica gel