Water → Benzeneethanamine, 4-chloro-N-(2-chloropropyl)-, hydrochloride (1:1)

Temperature

42.5 °C

N,N-Dimethylacetamide (DMA), 0.614 mL, 6.60 mmol, 0.301 eq) was added to the substantially water-free mixture of intermediate 1-(4-chlorophenethylamino)propan-2-ol in toluene as it was stirred under nitrogen at 40-45° C. Thionyl chloride (2.04 mL, 28.0 mmol, 1.274 eq) was then added while the stirred mixture was maintained at 50-60° C. The stirred reaction mixture was then heated at 62° C. for three hours. LC/MS analysis of the crude reaction mixture indicated that conversion of the intermediate 1-(4-chlorophenethyl-amino)propan-2-ol was substantially complete after two hours. After the reaction mixture had been cooled to 0-5° C., isopropanol (5 mL) was added while the stirred product mixture was maintained at 0-5° C. Stirring at that temperature was continued for 2-3 hours, and then toluene (5 mL) was added to the suspension. After the resulting mixture had been heated to 60° C. for 30 minutes, the solid product was recovered by filtration, washing with isopropanol (2×5 mL), and vacuum drying at 72° C. overnight to provide off-white solid 2-chloro-N-(4-chlorophenethyl)propan-1-amine hydrochloride (4.38 g, 74.3% yield, 99.60% purity by HPLC peak area).

1. temperaturewas maintained at 50-60° C
2. customThe stirred reaction mixture
3. temperaturewas then heated at 62° C. for three hours
4. customLC/MS analysis of the crude reaction mixture
5. temperatureAfter the reaction mixture had been cooled to 0-5° C.
6. temperaturewas maintained at 0-5° C
7. stirringStirring at that temperature
8. waitwas continued for 2-3 hours
9. temperatureAfter the resulting mixture had been heated to 60° C. for 30 minutes
10. filtrationthe solid product was recovered by filtration
11. washwashing with isopropanol (2×5 mL), and vacuum
12. customdrying at 72° C. overnight

ORD record

ord-6e2d659b68144bcfae21c24da13c04f4

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08299241B2