N-(2-氯乙基)-N-甲基苯胺

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of compound 2b (500 mg, 2.95 mmol), K2CO3 (815 mg, 5.9 mmol), and KI (480 mg, 2.95 mmol) in DMF (50 mL) was bubbled with argon for 10 min Hydroquinone (649 mg, 5.9 mmol) was added to the mixture under argon. The reaction mixture was heated and stirred at 80° C. for 6 hr. After cooling to room temperature, the solvent was evaporated and the residue was quenched with 100 mL water. The mixture was adjusted pH to ˜7 with diluted hydrochloric acid. The mixture was then extracted with CH2Cl2 and the combined organic layer was washed with water and then brine and was dried over Na2SO4. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane/EtOAc to provide compound 2 as a white solid (143 mg, 0.59 mmol, 20% yield). HRMS (ESI, positive) m/z calcd. for C15H18NO2 [M+H]+: 244.13321, found: 244.13323. 1H NMR (400 MHz, Chloroform-d) δ 7.29 (ddd, J=7.3, 5.6, 2.0 Hz, 2H), 6.84-6.72 (m, 7H), 4.98 (broad s, 1H), 4.11 (t, J=6.1 Hz, 2H), 3.76 (t, J=6.1 Hz, 2H), 3.08 (s, 3H). was added to the mixture under argon The reaction mixture was heated After cooling to room temperature the solvent was evaporated the residue was quenched with 100 mL water The mixture was then extracted with CH2Cl2 the combined organic layer was washed with water brine and was dried over Na2SO4 The solvent was evaporated the residue was purified by silica gel column chromatography with hexane/EtOAc

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a mixture of compound 2a (1.25 g, 8.3 mmol) and CH2Cl2 (50 mL), SOCl2 (1.2 mls, 16.5 mmol) was added dropwise over 20 min. During addition the solution turned from colorless to yellow. After the addition was complete, the mixture was heated to reflux for one hour. After cooling to room temperature, the mixture was quenched carefully with cold, saturated aqueous K2CO3 (50 mL). The mixture was then extracted with CH2Cl2, and the combined organic layer was washed with brine and dried over Na2SO4. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane/EtOAc to provide the compound 2b (0.55 g, 3.2 mmol, 39.3% yield) as a yellow oil. HRMS (ESI, positive) m/z calcd. for C9H13ClN [M+H]+: 170.07310, found: 170.07309. 1H NMR (400 MHz, Chloroform-d) δ 7.24 (dd, J=8.8, 7.3 Hz, 2H), 6.73 (m, J=14.2, 7.6 Hz, 3H), 3.71-3.56 (m, 4H), 3.00 (s, 3H). was added dropwise over 20 min During addition the solution After the addition the mixture was heated to reflux for one hour the mixture was quenched carefully with cold, saturated aqueous K2CO3 (50 mL) The mixture was then extracted with CH2Cl2 the combined organic layer was washed with brine dried over Na2SO4 The solvent was evaporated the residue was purified by silica gel column chromatography with hexane/EtOAc

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a mixture of compound 2a (1.25 g, 8.3 mmol) and CH2Cl2 (50 mL), SOCl2 (1.2 mls, 16.5 mmol) was added dropwise over 20 min. During addition the solution turned from colorless to yellow. After the addition was complete, the mixture was heated to reflux for one hour. After cooling to room temperature, the mixture was quenched carefully with cold, saturated aqueous K2CO3 (50 mL). The mixture was then extracted with CH2Cl2, and the combined organic layer was washed with brine and dried over Na2SO4. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane/EtOAc to provide the compound 2b (0.55 g, 3.2 mmol, 39.3% yield) as a yellow oil. HRMS (ESI, positive) m/z calcd. for C9H13ClN [M+H]+: 170.07310, found: 170.07309. 1H NMR (400 MHz, Chloroform-d) δ 7.24 (dd, J=8.8, 7.3 Hz, 2H), 6.73 (m, J=14.2, 7.6 Hz, 3H), 3.71-3.56 (m, 4H), 3.00 (s, 3H). was added dropwise over 20 min During addition the solution After the addition the mixture was heated to reflux for one hour the mixture was quenched carefully with cold, saturated aqueous K2CO3 (50 mL) The mixture was then extracted with CH2Cl2 the combined organic layer was washed with brine dried over Na2SO4 The solvent was evaporated the residue was purified by silica gel column chromatography with hexane/EtOAc

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of compound 2b (500 mg, 2.95 mmol), K2CO3 (815 mg, 5.9 mmol), and KI (480 mg, 2.95 mmol) in DMF (50 mL) was bubbled with argon for 10 min Hydroquinone (649 mg, 5.9 mmol) was added to the mixture under argon. The reaction mixture was heated and stirred at 80° C. for 6 hr. After cooling to room temperature, the solvent was evaporated and the residue was quenched with 100 mL water. The mixture was adjusted pH to ˜7 with diluted hydrochloric acid. The mixture was then extracted with CH2Cl2 and the combined organic layer was washed with water and then brine and was dried over Na2SO4. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane/EtOAc to provide compound 2 as a white solid (143 mg, 0.59 mmol, 20% yield). HRMS (ESI, positive) m/z calcd. for C15H18NO2 [M+H]+: 244.13321, found: 244.13323. 1H NMR (400 MHz, Chloroform-d) δ 7.29 (ddd, J=7.3, 5.6, 2.0 Hz, 2H), 6.84-6.72 (m, 7H), 4.98 (broad s, 1H), 4.11 (t, J=6.1 Hz, 2H), 3.76 (t, J=6.1 Hz, 2H), 3.08 (s, 3H). was added to the mixture under argon The reaction mixture was heated After cooling to room temperature the solvent was evaporated the residue was quenched with 100 mL water The mixture was then extracted with CH2Cl2 the combined organic layer was washed with water brine and was dried over Na2SO4 The solvent was evaporated the residue was purified by silica gel column chromatography with hexane/EtOAc

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a mixture of compound 2a (1.25 g, 8.3 mmol) and CH2Cl2 (50 mL), SOCl2 (1.2 mls, 16.5 mmol) was added dropwise over 20 min. During addition the solution turned from colorless to yellow. After the addition was complete, the mixture was heated to reflux for one hour. After cooling to room temperature, the mixture was quenched carefully with cold, saturated aqueous K2CO3 (50 mL). The mixture was then extracted with CH2Cl2, and the combined organic layer was washed with brine and dried over Na2SO4. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane/EtOAc to provide the compound 2b (0.55 g, 3.2 mmol, 39.3% yield) as a yellow oil. HRMS (ESI, positive) m/z calcd. for C9H13ClN [M+H]+: 170.07310, found: 170.07309. 1H NMR (400 MHz, Chloroform-d) δ 7.24 (dd, J=8.8, 7.3 Hz, 2H), 6.73 (m, J=14.2, 7.6 Hz, 3H), 3.71-3.56 (m, 4H), 3.00 (s, 3H). was added dropwise over 20 min During addition the solution After the addition the mixture was heated to reflux for one hour the mixture was quenched carefully with cold, saturated aqueous K2CO3 (50 mL) The mixture was then extracted with CH2Cl2 the combined organic layer was washed with brine dried over Na2SO4 The solvent was evaporated the residue was purified by silica gel column chromatography with hexane/EtOAc