Diisopropylethylamine → Benzyl (2s,3s)-2-(2-(2-(3-ethylureido)-5-(trifluoromethyl)benzamido)acetamido)-3-hydroxyhex-4-ynylcarbamate

Participants

Reaction Steps

A solution of benzyl (2S,3S)-2-[2-(tert-butoxycarbonylamino)acetamido]-3-hydroxyhex-4-ynylcarbamate (315 mg; see WO-02/50019 for preparation) in methylene chloride (6 mL) was cooled to 0° C. and charged with trifluoroacetic acid (2 mL). The mixture was allowed to warm to RT and stirred for 45 min before being concentrated in vacuo. The residue was dissolved in methylene chloride and the resultant solution concentrated; this was repeated twice more to afford the TFA salt of (2S,3S)-2-(2-aminoacetamido)-3-hydroxyhex-4-ynylcarbamate, MS found: (M+H)+=320.6. A solution of this amine in CH2Cl2 (8 mL) was charged successively with N,N-diisopropylethylamine (0.66 mL), 2-(3-ethylureido)-5-(trifluoromethyl)benzoic acid (208 mg, see WO-02/50019), and BOP (399 mg). The reaction was stirred for 14 h at RT before being partitioned between EtOAc and water. The organic phase was washed with sat. NH4Cl, water, and brine before being dried (Na2SO4), filtered, and concentrated in vacuo. Flash chromatography provided benzyl (2S,3S)-2-(2-(2-(3-ethylureido)-5-(trifluoromethyl)benzamido)acetamido)-3-hydroxyhex-4-ynylcarbamate (167 mg). MS found: (M+H)+=578.5.

Provenance & Evidence