1-(bromomethyl)-4-(2-methylpropyl)benzene

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: A mixture of 4-hydroxy-2,3-dimethyl-benzaldehyde (220 mg), 4-isobutylbenzyl bromide (341 mg), potassium carbonate (1.38 g) and ethyl methyl ketone (10 ml) was refluxed for 6 hrs. After cooling, the reaction mixture was diluted with ethyl acetate, the solution was washed with dil hydrochloric acid, water, successively, dried and evaporated. The residue was purified by column chromatography on silica gel (hexane:EtOAc=10:1) to give the title compound (383 mg) having the following physical data: was refluxed for 6 hrs After cooling the solution was washed with dil hydrochloric acid, water successively, dried evaporated The residue was purified by column chromatography on silica gel (hexane:EtOAc=10:1)

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

実験手順: HBr gas was bubbled through a solution of (4-isobutyl-phenyl)-methanol (5 g, 28 mmol) in Et2O (50 mL) for 10–15 minutes. The reaction was stirred for 1 h and was poured onto ice (100 g). Et2O was added and the organic solution was washed with brine (2×). The organic solution was dried (MgSO4), filtered, and concentrated to provide the title compound (6 g). 1H NMR (400 MHz, CDCl3) δ 7.28 (d, 2H), 7.10 (d, 2H), 4.49 (s, 2H), 2.45 (d, 2H), 1.84 (m, 1H), 0.89 (d, 6H). was poured onto ice (100 g) the organic solution was washed with brine (2×) The organic solution was dried (MgSO4) filtered concentrated

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

実験手順: HBr gas was bubbled through a solution of (4-isobutyl-phenyl)-methanol (5 g, 28 mmol) in Et2O (50 mL) for 10–15 minutes. The reaction was stirred for 1 h and was poured onto ice (100 g). Et2O was added and the organic solution was washed with brine (2×). The organic solution was dried (MgSO4), filtered, and concentrated to provide the title compound (6 g). 1H NMR (400 MHz, CDCl3) δ 7.28 (d, 2H), 7.10 (d, 2H), 4.49 (s, 2H), 2.45 (d, 2H), 1.84 (m, 1H), 0.89 (d, 6H). was poured onto ice (100 g) the organic solution was washed with brine (2×) The organic solution was dried (MgSO4) filtered concentrated

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

実験手順: In a similar manner to Example 8, (2S,4S)-1-[[N-(4-carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (30.0 mg) and 4-(2,2-dimethylethyl)benzyl bromide (23.2 mg) were used to obtain (2S,4S)-1-[[N-[4-[4-(2,2-dimethylethyl)benzyl]oxycarbonyl bicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (29.9 mg).

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

実験手順: In a similar manner to Example 8, (2S,4S)-1-[[N-(4-carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (30.0 mg) and 4-(2,2-dimethylethyl)benzyl bromide (23.2 mg) were used to obtain (2S,4S)-1-[[N-[4-[4-(2,2-dimethylethyl)benzyl]oxycarbonyl bicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (29.9 mg).

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: A mixture of 4-hydroxy-2,3-dimethylbenzaldehyde (220 mg), 4-isobutylbenzyl bromide (341 mg), potassium carbonate (1.38 g) and ethyl methyl ketone (10 ml) was refluxed for 6 hrs. After cooling, the reaction mixture was diluted with ethyl acetate, the solution was washed with dil hydrochloric acid, water, successively, dried and evaporated. The residue was purified by column chromatography on silica gel (hexane:EtOAc=10:1) to give the title compound (383 mg) having the following physical data: was refluxed for 6 hrs After cooling the solution was washed with dil hydrochloric acid, water successively, dried evaporated The residue was purified by column chromatography on silica gel (hexane:EtOAc=10:1)

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

実験手順: In a similar manner to Example 8, (2S,4S)-1-[[N-(4-carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (30.0 mg) and 4-(2,2-dimethylethyl)benzyl bromide (23.2 mg) were used to obtain (2S,4S)-1-[[N-[4-[4-(2,2-dimethylethyl)benzyl]oxycarbonyl bicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (29.9 mg).

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

実験手順: In a similar manner to Example 8, (2S,4S)-1-[[N-(4-carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (30.0 mg) and 4-(2,2-dimethylethyl)benzyl bromide (23.2 mg) were used to obtain (2S,4S)-1-[[N-[4-[4-(2,2-dimethylethyl)benzyl]oxycarbonyl bicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (29.9 mg).

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

実験手順: HBr gas was bubbled through a solution of (4-isobutyl-phenyl)-methanol (5 g, 28 mmol) in Et2O (50 mL) for 10-15 minutes. The reaction was stirred for 1 h and was poured onto ice (100 g). Et2O was added and the organic solution was washed with brine (2×). The organic solution was dried (MgSO4), filtered, and concentrated to provide the title compound (6 g). 1H NMR (400 MHz, CDCl3) δ 7.28 (d, 2H), 7.10 (d, 2H), 4.49 (s, 2H), 2.45 (d, 2H), 1.84 (m, 1H), 0.89 (d, 6H). was poured onto ice (100 g) the organic solution was washed with brine (2×) The organic solution was dried (MgSO4) filtered concentrated

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

実験手順: HBr gas was bubbled through a solution of (4-isobutyl-phenyl)-methanol (5 g, 28 mmol) in Et2O (50 mL) for 10-15 minutes. The reaction was stirred for 1 h and was poured onto ice (100 g). Et2O was added and the organic solution was washed with brine (2×). The organic solution was dried (MgSO4), filtered, and concentrated to provide the title compound (6 g). 1H NMR (400 MHz, CDCl3) δ 7.28 (d, 2H), 7.10 (d, 2H), 4.49 (s, 2H), 2.45 (d, 2H), 1.84 (m, 1H), 0.89 (d, 6H). was poured onto ice (100 g) the organic solution was washed with brine (2×) The organic solution was dried (MgSO4) filtered concentrated