4,4-Dimethyl-2-pentyne

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

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

Procedure: To a solution of N-(2-bromo-3-fluorophenyl)butyramide (2.0 g, 7.0 mmol) in Et3N (100 mL) was added 4,4-dimethylpent-2-yne (6.0 g, 60 mmol), CuI (70 mg, 3.8 mmol), and Pd(PPh3)2Cl2 (500 mg) successively at room temperature under N2. The mixture was heated at 80° C. overnight. The cooled mixture was filtered and the filtrate was extracted with EtOAc (40 mL×3). The organic layers were washed with sat. NaCl, dried over anhydrous Na2SO4, and evaporated under vacuum. The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether) to give N-(2-(3,3-dimethylbut-1-ynyl)-3-fluorophenyl)butyramide (1.1 g, 55%). 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J=7.6, 1H), 7.95 (s, 1H), 7.21 (m, 1H), 6.77 (t, J=7.6 Hz, 1H), 2.39 (t, J=7.6 Hz, 2H), 1.82-1.75 (m, 2H), 1.40 (s, 9H), 1.12 (t, J=7.2 Hz, 3H). The cooled mixture was filtered the filtrate was extracted with EtOAc (40 mL×3) The organic layers were washed with sat. NaCl dried over anhydrous Na2SO4 evaporated under vacuum The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether)

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

Procedure: To a solution of N-(2-bromo-3-fluorophenyl)butyramide (2.0 g, 7.0 mmol) in Et3N (100 mL) was added 4,4-dimethylpent-2-yne (6.0 g, 60 mmol), CuI (70 mg, 3.8 mmol), and Pd(PPh3)2Cl2 (500 mg) successively at room temperature under N2. The mixture was heated at 80° C. overnight. The cooled mixture was filtered and the filtrate was extracted with EtOAc (40 mL×3). The organic layers were washed with sat. NaCl, dried over anhydrous Na2SO4, and evaporated under vacuum. The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether) to give N-(2-(3,3-dimethylbut-1-ynyl)-3-fluorophenyl)butyramide (1.1 g, 55%). 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J=7.6, 1H), 7.95 (s, 1H), 7.21 (m, 1H), 6.77 (t, J=7.6 Hz, 1H), 2.39 (t, J=7.6 Hz, 2 fl), 1.82-1.75 (m, 2H), 1.40 (s, 9H), 1.12 (t, J=7.2 Hz, 3H). The cooled mixture was filtered the filtrate was extracted with EtOAc (40 mL×3) The organic layers were washed with sat. NaCl dried over anhydrous Na2SO4 evaporated under vacuum The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether)

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

Procedure: To a solution of N-(2-bromo-3-fluorophenyl)butyramide (2.0 g, 7.0 mmol) in Et3N (100 mL) was added 4,4-dimethylpent-2-yne (6.0 g, 60 mmol), CuI (70 mg, 3.8 mmol), and Pd(PPh3)2Cl2 (500 mg) successively at room temperature under N2. The mixture was heated at 80° C. overnight. The cooled mixture was filtered and the filtrate was extracted with EtOAc (40 mL×3). The organic layers were washed with sat. NaCl, dried over anhydrous Na2SO4, and evaporated under vacuum. The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether) to give N-(2-(3,3-dimethylbut-1-ynyl)-3-fluorophenyl)butyramide (1.1 g, 55%). 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J=7.6, 1H), 7.95 (s, 1H), 7.21 (m, 1H), 6.77 (t, J=7.6 Hz, 1H), 2.39 (t, J=7.6 Hz, 2 fl), 1.82-1.75 (m, 2H), 1.40 (s, 9H), 1.12 (t, J=7.2 Hz, 3H). The cooled mixture was filtered the filtrate was extracted with EtOAc (40 mL×3) The organic layers were washed with sat. NaCl dried over anhydrous Na2SO4 evaporated under vacuum The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether)

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

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

Procedure: To a solution of N-(2-bromo-3-fluorophenyl)butyramide (2.0 g, 7.0 mmol) in Et3N (100 mL) was added 4,4-dimethylpent-2-yne (6.0 g, 60 mmol), CuI (70 mg, 3.8 mmol), and Pd(PPh3)2Cl2 (500 mg) successively at room temperature under N2. The mixture was heated at 80° C. overnight. The cooled mixture was filtered and the filtrate was extracted with EtOAc (40 mL×3). The organic layers were washed with sat. NaCl, dried over anhydrous Na2SO4, and evaporated under vacuum. The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether) to give N-(2-(3,3-dimethylbut-1-ynyl)-3-fluorophenyl)butyramide (1.1 g, 55%). 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J=7.6, 1 H), 7.95 (s, 1 H), 7.21 (m, 1 H), 6.77 (t, J=7.6 Hz, 1 H), 2.39 (t, J=7.6 Hz, 2 H), 1.82-1.75 (m, 2H), 1.40 (s, 9 H), 1.12 (t, J=7.2 Hz, 3 H). The cooled mixture was filtered the filtrate was extracted with EtOAc (40 mL×3) The organic layers were washed with sat. NaCl dried over anhydrous Na2SO4 evaporated under vacuum The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether)

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

Procedure: To a solution of N-(2-bromo-3-fluorophenyl)butyramide (2.0 g, 7.0 mmol) in Et3N (100 mL) was added 4,4-dimethylpent-2-yne (6.0 g, 60 mmol), CuI (70 mg, 3.8 mmol), and Pd(PPh3)2Cl2 (500 mg) successively at room temperature under N2. The mixture was heated at 80° C. overnight. The cooled mixture was filtered and the filtrate was extracted with EtOAc (40 mL×3). The organic layers were washed with sat. NaCl, dried over anhydrous Na2SO4, and evaporated under vacuum. The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether) to give N-(2-(3,3-dimethylbut-1-ynyl)-3-fluorophenyl)butyramide (1.1 g, 55%). 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J=7.6, 1H), 7.95 (s, 1H), 7.21 (m, 1H), 6.77 (t, J=7.6 Hz, 1H), 2.39 (t, J=7.6 Hz, 2H), 1.82-1.75 (m, 2H), 1.40 (s, 9H), 1.12 (t, J=7.2 Hz, 3H). The cooled mixture was filtered the filtrate was extracted with EtOAc (40 mL×3) The organic layers were washed with sat. NaCl dried over anhydrous Na2SO4 evaporated under vacuum The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether)

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

Procedure: To a solution of N-(2-bromo-3-fluorophenyl)butyramide (2.0 g, 7.0 mmol) in Et3N (100 mL) was added 4,4-dimethylpent-2-yne (6.0 g, 60 mmol), CuI (70 mg, 3.8 mmol), and Pd(PPh3)2Cl2 (500 mg) successively at room temperature under N2. The mixture was heated at 80° C. overnight. The cooled mixture was filtered and the filtrate was extracted with EtOAc (40 mL×3). The organic layers were washed with sat. NaCl, dried over anhydrous Na2SO4, and evaporated under vacuum. The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether) to give N-(2-(3,3-dimethylbut-1-ynyl)-3-fluorophenyl)butyramide (1.1 g, 55%). NMR (400 MHz, CDCl3) δ 8.20 (d, J=7.6, 1 H), 7.95 (s, 1 H), 7.21 (m, 1 H), 6.77 (t, J=7.6 Hz, 1 H), 2.39 (t, J=7.6 Hz, 2 H), 1.82-1.75 (m, 2H), 1.40 (s, 9 H), 1.12 (t, J=7.2 Hz, 3 H). The cooled mixture was filtered the filtrate was extracted with EtOAc (40 mL×3) The organic layers were washed with sat. NaCl dried over anhydrous Na2SO4 evaporated under vacuum The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether)

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

Procedure: To a solution of N-(2-bromo-3-fluorophenyl)butyramide (2.0 g, 7.0 mmol) in Et3N (100 mL) was added 4,4-dimethylpent-2-yne (6.0 g, 60 mmol), CuI (70 mg, 3.8 mmol), and Pd(PPh3)2Cl2 (500 mg) successively at room temperature under N2. The mixture was heated at 80° C. overnight. The cooled mixture was filtered and the filtrate was extracted with EtOAc (40 mL×3). The organic layers were washed with sat. NaCl, dried over anhydrous Na2SO4, and evaporated under vacuum. The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether) to give N-(2-(3,3-dimethylbut-1-ynyl)-3-fluorophenyl)butyramide (1.1 g, 55%). 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J=7.6, 1H), 7.95 (s, 1H), 7.21 (m, 1H), 6.77 (t, J=7.6 Hz, 1H), 2.39 (t, J=7.6 Hz, 2H), 1.82-1.75 (m, 2H), 1.40 (s, 9H), 1.12 (t, J=7.2 Hz, 3H). The cooled mixture was filtered the filtrate was extracted with EtOAc (40 mL×3) The organic layers were washed with sat. NaCl dried over anhydrous Na2SO4 evaporated under vacuum The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether)

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

Procedure: To a solution of N-(2-bromo-3-fluorophenyl)butyramide (2.0 g, 7.0 mmol) in Et3N (100 mL) was added 4,4-dimethylpent-2-yne (6.0 g, 60 mmol), CuI (70 mg, 3.8 mmol), and Pd(PPh3)2Cl2 (500 mg) successively at room temperature under N2. The mixture was heated at 80° C. overnight. The cooled mixture was filtered and the filtrate was extracted with EtOAc (40 mL×3). The organic layers were washed with sat. NaCl, dried over anhydrous Na2SO4, and evaporated under vacuum. The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether) to give N-(2-(3,3-dimethylbut-1-ynyl)-3-fluorophenyl)butyramide (1.1 g, 55%). 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J=7.6, 1H), 7.95 (s, 1H), 7.21 (m, 1H), 6.77 (t, J=7.6 Hz, 1H), 2.39 (t, J=7.6 Hz, 2H), 1.82-1.75 (m, 2H), 1.40 (s, 9H), 1.12 (t, J=7.2 Hz, 3H). The cooled mixture was filtered the filtrate was extracted with EtOAc (40 mL×3) The organic layers were washed with sat. NaCl dried over anhydrous Na2SO4 evaporated under vacuum The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether)

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

Procedure: To a solution of N-(2-bromo-3-fluorophenyl)butyramide (2.0 g, 7.0 mmol) in Et3N (100 mL) was added 4,4-dimethylpent-2-yne (6.0 g, 60 mmol), CuI (70 mg, 3.8 mmol), and Pd(PPh3)2Cl2 (500 mg) successively at room temperature under N2. The mixture was heated at 80° C. overnight. The cooled mixture was filtered and the filtrate was extracted with EtOAc (40 mL×3). The organic layers were washed with sat. NaCl, dried over anhydrous Na2SO4, and evaporated under vacuum. The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether) to give N-(2-(3,3-dimethylbut-1-ynyl)-3-fluorophenyl)butyramide (1.1 g, 55%). 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J=7.6, 1H), 7.95 (s, 1H), 7.21 (m, 1H), 6.77 (t, J=7.6 Hz, 1H), 2.39 (t, J=7.6 Hz, 2H), 1.82-1.75 (m, 2H), 1.40 (s, 9H), 1.12 (t, J=7.2 Hz, 3H). The cooled mixture was filtered the filtrate was extracted with EtOAc (40 mL×3) The organic layers were washed with sat. NaCl dried over anhydrous Na2SO4 evaporated under vacuum The crude compound was purified by column chromatography on silica gel (10% EtOAc in petroleum ether)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Bromo-5-methoxyaniline (1.01 g; synthesized according to the process reported by J. H. Tidwell et al., J. Am. Chem. Soc., vol. 116, pp. 11797-11810 (1994)), 2,2-dimethyl-3-pentyne (480 mg; mfd. by Chemsampco), palladium acetate (28.1 mg), tetra-n-butylammonium chloride (1.39 g; mfd. by TOKYO KASEI), potassium carbonate (3.45 g) and triphenylphosphine (65.6 mg) were dissolved in N,N-dimethylacetamide (50 mL). After stirring at 100° C. for 20 hours, the reaction mixture was diluted with water and extracted with ether. The organic layer was washed with a saturated aqueous ammonium chloride solution and water, and then dried. The solvent was distilled off under reduced pressure. The residue was purified twice by silica gel column chromatography (5:1 hexane/ethyl acetate) to yield the title compound (202 mg). synthesized extracted with ether The organic layer was washed with a saturated aqueous ammonium chloride solution and water dried The solvent was distilled off under reduced pressure The residue was purified twice by silica gel column chromatography (5:1 hexane/ethyl acetate)