Water → HCID 117870516, compound

(R)-2-amino-1-(4-fluoro-3-(trifluoromethyl)phenyl)ethanol (2.27 g, 10.2 mmol) was dissolved in 50 mL of dichloromethane. Water (50 mL) containing sodium bicarbonate (1.11 g, 13.2 mmol) was added. The mixture was stirred under ice bath and 2-chloroacetyl chloride (1.38 g, 12.2 mmol) in dichloromethane (10 mL) was added dropwise. The mixture was stirred for 20 min. The pH value was checked and concentrated sodium bicarbonate solution was added (15 mL) to adjust pH to basic. The ice bath was removed and the mixture was stirred for 15 min. TLC indicated consumption of the starting material. The mixture was extracted with dichloromethane and sodium bicarbonate solution. The organic layer was washed with brine and dried. Solvents were evaporated and the resulting material was purified through ISCO flash column chromatography (40 g silica gel, 20% to 90% ethyl acetate in hexanes gradient) to give 2-chloro-N—[(R)-2-(4-fluoro-3-trifluoromethylphenyl)-2-hydroxy-ethyl]-acetamide as an oily material, which gradually solidified (2.64 g). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.18 (br. s., 1H) 3.40 (ddd, J=14.07, 8.21, 5.29 Hz, 1H) 3.72 (ddd, J=14.16, 6.99, 3.40 Hz, 1H) 4.09 (s, 2H) 4.95 (dd, J=7.93, 3.02 Hz, 1H) 7.03 (br. s., 1H) 7.16-7.26 (m, 1H) 7.54-7.62 (m, 1H) 7.66 (dd, J=6.61, 2.08 Hz, 1H).

1. additionwas added
2. stirringThe mixture was stirred for 20 min
3. customThe ice bath was removed
4. stirringthe mixture was stirred for 15 min
5. customconsumption of the starting material
6. extractionThe mixture was extracted with dichloromethane and sodium bicarbonate solution
7. washThe organic layer was washed with brine
8. customdried
9. customSolvents were evaporated
10. customthe resulting material was purified through ISCO flash column chromatography (40 g silica gel, 20% to 90% ethyl acetate in hexanes gradient)

ORD record

ord-285e757391d44bb099e1ce03d74f3bd2

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09353096B2