Trifluoroacetic acid → HCID 86661747, compound

Participants

Reaction Conditions

Reaction Steps

(S)-3-diisopropylphosphonoformamido-2-(tritylamino)propanol (10.49 g, 20 mmol) was dissolved in a mixture of chloroform-methanol (1:1, 40 mL) and cooled to 0° C. in an ice bath. The reaction mixture was stirred at RT for 7 h, after dropwise addition of trifluoroacetic acid (20.0 mmol, 1.5 mL) at 0° C. The solvents were removed and the resulting residue was azeotroped 5 times with diethyl ether (5×40 mL) and partitioned between diethyl ether (150 mL) and water (50 mL). The ether layer was washed with water (20 mL) and the combined aqueous fractions were basified with NaHCO3 (80 mmol, 6.72 g). Aqueous fraction was diluted with EtOAc (150 mL) and the mixture was cooled to 0° C. in an ice bath. Benzyl chloroformate (2.9 mL, 20 mmol) was then added to the reaction mixture at 0° C. and stirred vigorously at RT for 1.5 h. The layers were separated and the aqueous layer was washed with EtOAc (2×30 mL). The combined organic fractions were washed with brine (40 mL), dried over anhydrous Na2SO4 and concentrated. The residue was purified by column chromatography (silica gel, 5% MeOH in EtOAc) to afford (S)-2-benzyloxycarbonylamino 3-(diisopropy-lphosphonoformamido)propanol as gummy solid in 50% (4.16 g) yield.

Provenance & Evidence