Triethylamine → (2,2,2-Trichloroethoxycarbonyl)lysine

Temperature

20 °C

Nα -(1,1-Dimethylethoxycarbonyl)-Nε -(2,2,2-trichloroethoxycarbonyl)lysine. In a modification of a literature method [Yajima, H.; Watanabe, H.; Okamoto, M., Studies on peptides. XXXIII. Nε -β,β,β-Trichloroethyloxycarbonyllysine, Chem. Pharm. Bull, 1971, 19, 2185-2189], lysine monohydrochloride (9.14 g, 50 mmol) was stirred under reflux with copper (II) carbonate (21.6 g, 75 mmol) in water (180 mL) for 3 h. The solution was filtered while hot and the filtrate was cooled to 20° C. 2,2,2-Trichloroethyl chloroformate (15.9 g, 75 mmol) and aqueous sodium carbonate (13.3 g, 125 mmol in 40 mL) were added alternately in portions to the filtrate during 30 min and the mixture was stirred vigorously at 0° C. for 20 h. The blue precipitate was collected and was boiled under reflux with ethylenediaminetetraacetic acid disodium salt (18.6 g, 100 mmol) in water (200 mL) for 2 h. The solution was cooled to 0° C. for 20 hrs and crude Nε -(2,2,2-trichloroethoxycarbonyl)lysine was collected as a gummy solid. This material was dissolved in water (75 mL) and triethylamine (20.2 g, 200 mmol) was added, followed by di-t-butyl dicarbonate (13.64 g, 62 mmol) and 1,4-dioxan (30 mL). The mixture was stirred vigorously for 3 d. The mixture was washed with diethyl ether. Ethyl acetate was added to the aqueous phase and the mixture was acidified by careful addition of cold 10% aqueous sulphuric acid. The ethyl acetate phase was washed with water and dried with anhydrous magnesium sulphate. The solvent was evaporated under reduced pressure to give Nα -(1,1-dimethylethoxycarbonyl)-Ne -(2,2,2-trichloroethoxycarbonyl)lysine (12.32 g, 55%).

1. filtrationThe solution was filtered while hot and the filtrate
2. customThe blue precipitate was collected
3. temperatureThe solution was cooled to 0° C. for 20 hrs
4. customcrude Nε -(2,2,2-trichloroethoxycarbonyl)lysine was collected as a gummy solid
5. dissolutionThis material was dissolved in water (75 mL)
6. stirringThe mixture was stirred vigorously for 3 d
7. washThe mixture was washed with diethyl ether
8. additionEthyl acetate was added to the aqueous phase
9. additionthe mixture was acidified by careful addition of cold 10% aqueous sulphuric acid
10. washThe ethyl acetate phase was washed with water
11. dry with materialdried with anhydrous magnesium sulphate
12. customThe solvent was evaporated under reduced pressure

ORD record

ord-c5af9701f63d472db954b914499ef083

Source dataset

uspto-grants-1997_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05618528