Ethanamine, 2,2,2-trifluoro- → N-methyl-N-((1R)-2-phenyl-1-((2,2,2-trifluoroethyl)carbamoyl)ethyl)carbamic acid tert-butyl ester

Temperature

0 °C

At 0° C., N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (2.18 g, 11.4 mmol) was added to a solution of (2R)-2-(N-(tert-butoxycarbonyl)-N-methylamino)-3-phenylpropionic acid (3.0 g, 11.4 mmol) and 1-hydroxybenzotriazole hydrate (1.54 g, 11.4 mmol) in N,N-dimethylformamide (2 ml) and dichloromethane (4 ml). The reaction mixture was stirred for 15 min at 0° C. 2,2,2-Trifluoroethylamine (0.91 ml, 11.4 mmol) and ethyldiisopropylamine (2.0 ml, 11.39 mmol) were added successively. The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (150 ml) and washed with 10% aqueous sodium hydrogen sulfate solution (200 ml). The aqueous phase was extracted with ethyl acetate (2×30 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (150 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (240 g), using ethyl acetate/heptane 1:2 as eluent, to give 3.52 g of N-methyl-N-((1R)-2-phenyl-1-((2,2,2-trifluoroethyl)carbamoyl)ethyl)carbamic acid tert-butyl ester.

1. stirringThe reaction mixture was stirred for 16 h, while it
2. temperaturewas warming up to room temperature
3. washwashed with 10% aqueous sodium hydrogen sulfate solution (200 ml)
4. extractionThe aqueous phase was extracted with ethyl acetate (2×30 ml)
5. washThe combined organic layers were washed with saturated sodium hydrogen carbonate solution (150 ml)
6. dry with materialdried over magnesium sulfate
7. customThe solvent was removed in vacuo
8. customThe crude product was purified by flash chromatography on silica (240 g)

ORD record

ord-1e8c77db1fa74de68cdd4012e2bbcf02

Source dataset

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06939880B2