Tetrahydrofuran → (R)-ethyl 5-(benzyloxycarbonylamino)-2-(3-(4-(tert-butoxycarbonylamino)benzyl)ureido)pentanoate

Participants

Reaction Conditions

Reaction Steps

(R)-ethyl 2-amino-5-(benzyloxycarbonylamino)pentanoate (1 equivalent, 146 mg, 0.50 mmol) was dissolved in anhydrous THF (4 mL) and trisphosgene (0.33 equivalent, 49 mg, 0.17 mmol) was added while stirring at −10° C. The mixture was allowed to warm to room temperature, and then refluxed for 2 h. Tert-butyl-N-[4-(aminomethyl)phenyl]carbamate (1 equivalent, 110 mg, 0.50 mmol) and triethylamine (2 equivalent, 138 μl, 1 mmol) were added successively and the resulting solution was stirring at room temperature overnight. The reaction mixture was concentrated, washed by 30 ml of NaHCO3 and extracted by 3×30 ml EtOAc. The organic phase was dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography (EDP/EtOAc) to afford the urea protected (146 mg, 54%) as a colourless oil Rf=0.59 (EtOAc). 1H NMR (300 MHz, CDCl3) δ 7.30-7.23 (s, 5H), 7.20 (d, J=8.4 Hz, 2H), 7.09 (d, J=8.4 Hz, 2H), 6.84-6.66 (m, 1H), 5.62-5.42 (m, 2H), 5.28-5.10 (m, 1H), 5.00 (s, 2H), 4.46-4.29 (m, 1H), 4.18 (d, J=5.5 Hz, 2H), 4.05 (q, J=7.1 Hz, 3H), 3.16-3.00 (m, 2H), 1.82-1.28 (m, 4H), 1.43 (s, 9H), 1.16 (t, J=7.2 Hz, 3H).

Provenance & Evidence