Thionyl Chloride → N-(2-Chloroethyl)-N-(propan-2-yl)aniline

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).

1. additionwas added dropwise over 20 min
2. additionAfter the addition
3. temperaturethe mixture was heated
4. temperatureto reflux for one hour
5. customthe mixture was quenched carefully with cold, saturated aqueous K2CO3 (100 mL)
6. extractionThe mixture was then extracted with CH2Cl2
7. washthe combined organic layer was washed with saturated aqueous K2CO3
8. washwashed with brine
9. dry with materialdried over Na2SO4
10. customThe solvent was evaporated
11. customthe residue was purified by silica gel column chromatography with hexane/EtOAc (8/1)

ORD record

ord-3244ab84a6b5438d9b46713bdd95861c

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394233B2