2-(N-propan-2-ylanilino)ethanol

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

Procedure: Compound 4a (617 mg, 4.6 mmol) was reacted with 2-Iodoethanol (0.54 mls, 6.9 mmol) and diisopropylethylamine (1.2 mls, 6.9 mmol) in ACN (20 mls) at 30° C. for 48 hours. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane and EtOAc to provide the intermediate 4b (483 mg, 2.7 mmol, 59% yield) as a light brown oil. HRMS (ESI, positive) m/z calcd. for C11H18N1O1 [M+H]+: 180.13829, found: 180.13829. 1H NMR (400 MHz, CDCl3) δ 7.28-7.19 (t, J=8.0 Hz, 2H), 6.92-6.85 (d, J=8.2 Hz, 2H), 6.83-6.75 (t, J=7.3 Hz, 1H), 4.03-3.88 (hept, J=6.6 Hz, 1H), 3.70-3.62 (t, J=6.2 Hz, 2H), 3.34-3.24 (m, 2H), 1.19-1.12 (d, J=6.6 Hz, 6H). The solvent was evaporated the residue was purified by silica gel column chromatography with hexane and EtOAc

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: Compound 4a (617 mg, 4.6 mmol) was reacted with 2-Iodoethanol (0.54 mls, 6.9 mmol) and diisopropylethylamine (1.2 mls, 6.9 mmol) in ACN (20 mls) at 30° C. for 48 hours. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane and EtOAc to provide the intermediate 4b (483 mg, 2.7 mmol, 59% yield) as a light brown oil. HRMS (ESI, positive) m/z calcd. for C11H18N1O1 [M+H]+: 180.13829, found: 180.13829. 1H NMR (400 MHz, CDCl3) δ 7.28-7.19 (t, J=8.0 Hz, 2H), 6.92-6.85 (d, J=8.2 Hz, 2H), 6.83-6.75 (t, J=7.3 Hz, 1H), 4.03-3.88 (hept, J=6.6 Hz, 1H), 3.70-3.62 (t, J=6.2 Hz, 2H), 3.34-3.24 (m, 2H), 1.19-1.12 (d, J=6.6 Hz, 6H). The solvent was evaporated the residue was purified by silica gel column chromatography with hexane and EtOAc