N-(2-chloroethyl)-N-propan-2-ylaniline

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

Procedure: A mixture of compound 4c (400 mg, 2 mmol), K2CO3 (558 mg, 4 mmol), and KI (720 mg, 4 mmol) in DMF (50 mL) was bubbled with argon for 10 min Hydroquinone (440 mg, 4 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 to provide compound 4 (210 mg, 0.77 mmol, 38.3% yield) as a brown oil. HRMS (ESI, positive) m/z calcd. for C17H22N1O2 [M+H]+: 272.16451, found: 272.16455. 1H NMR (400 MHz, CDCl3) δ 7.16-7.05 (m, 2H), 6.75-6.56 (m, 7H), 4.08-3.83 (m, 4H), 3.50-3.42 (t, J=7.1 Hz, 1H), 1.19-1.06 (m, 6H). 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

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

Procedure: In a mixture of compound 4b (483 mg, 2.7 mmol) and CH2Cl2 (50 mL), SOCl2 (0.24 ml, 3.2 mmol) was added dropwise over 20 min. 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 (100 mL). The mixture was then extracted with CH2Cl2, and the combined organic layer was washed with saturated aqueous K2CO3, washed with brine, and dried over Na2SO4. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane/EtOAc (8/1) to provide the intermediate 4c (170 mg, 0.86 mmol, 31.8% yield) as a yellow brown oil. 1H NMR (400 MHz, CDCl3) δ 7.35-7.26 (m, 2H), 6.86-6.76 (m, 3H), 4.19-4.04 (hept, J=6.5 Hz, 1H), 3.65-3.50 (td, J=12.6, 7.3 Hz, 4H), 1.29-1.22 (d, J=6.6 Hz, 6H). was added dropwise over 20 min After the addition the mixture was heated to reflux for one hour the mixture was quenched carefully with cold, saturated aqueous K2CO3 (100 mL) The mixture was then extracted with CH2Cl2 the combined organic layer was washed with saturated aqueous K2CO3 washed with brine dried over Na2SO4 The solvent was evaporated the residue was purified by silica gel column chromatography with hexane/EtOAc (8/1)

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

Procedure: In a mixture of compound 4b (483 mg, 2.7 mmol) and CH2Cl2 (50 mL), SOCl2 (0.24 ml, 3.2 mmol) was added dropwise over 20 min. 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 (100 mL). The mixture was then extracted with CH2Cl2, and the combined organic layer was washed with saturated aqueous K2CO3, washed with brine, and dried over Na2SO4. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane/EtOAc (8/1) to provide the intermediate 4c (170 mg, 0.86 mmol, 31.8% yield) as a yellow brown oil. 1H NMR (400 MHz, CDCl3) δ 7.35-7.26 (m, 2H), 6.86-6.76 (m, 3H), 4.19-4.04 (hept, J=6.5 Hz, 1H), 3.65-3.50 (td, J=12.6, 7.3 Hz, 4H), 1.29-1.22 (d, J=6.6 Hz, 6H). was added dropwise over 20 min After the addition the mixture was heated to reflux for one hour the mixture was quenched carefully with cold, saturated aqueous K2CO3 (100 mL) The mixture was then extracted with CH2Cl2 the combined organic layer was washed with saturated aqueous K2CO3 washed with brine dried over Na2SO4 The solvent was evaporated the residue was purified by silica gel column chromatography with hexane/EtOAc (8/1)

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

Procedure: A mixture of compound 4c (400 mg, 2 mmol), K2CO3 (558 mg, 4 mmol), and KI (720 mg, 4 mmol) in DMF (50 mL) was bubbled with argon for 10 min Hydroquinone (440 mg, 4 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 to provide compound 4 (210 mg, 0.77 mmol, 38.3% yield) as a brown oil. HRMS (ESI, positive) m/z calcd. for C17H22N1O2 [M+H]+: 272.16451, found: 272.16455. 1H NMR (400 MHz, CDCl3) δ 7.16-7.05 (m, 2H), 6.75-6.56 (m, 7H), 4.08-3.83 (m, 4H), 3.50-3.42 (t, J=7.1 Hz, 1H), 1.19-1.06 (m, 6H). 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

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

Procedure: In a mixture of compound 4b (483 mg, 2.7 mmol) and CH2Cl2 (50 mL), SOCl2 (0.24 ml, 3.2 mmol) was added dropwise over 20 min. 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 (100 mL). The mixture was then extracted with CH2Cl2, and the combined organic layer was washed with saturated aqueous K2CO3, washed with brine, and dried over Na2SO4. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane/EtOAc (8/1) to provide the intermediate 4c (170 mg, 0.86 mmol, 31.8% yield) as a yellow brown oil. 1H NMR (400 MHz, CDCl3) δ 7.35-7.26 (m, 2H), 6.86-6.76 (m, 3H), 4.19-4.04 (hept, J=6.5 Hz, 1H), 3.65-3.50 (td, J=12.6, 7.3 Hz, 4H), 1.29-1.22 (d, J=6.6 Hz, 6H). was added dropwise over 20 min After the addition the mixture was heated to reflux for one hour the mixture was quenched carefully with cold, saturated aqueous K2CO3 (100 mL) The mixture was then extracted with CH2Cl2 the combined organic layer was washed with saturated aqueous K2CO3 washed with brine dried over Na2SO4 The solvent was evaporated the residue was purified by silica gel column chromatography with hexane/EtOAc (8/1)