Diisopropylethylamine → (12S,15R)-benzyl 12-(tert-butoxycarbonylamino)-8-(2-(tert-butoxycarbonylamino)ethyl)-2,2-dimethyl-4,9,13-trioxo-15-(4-(trifluoromethyl)benzyl)-3-oxa-5,8,14-triazahexadecan-16-oate

Participants

Reaction Steps

To a suspension of (R)-benzyl 2-amino-3-(4-(trifluoromethyl)phenyl)propanoate (CLXV) (3 g, 8.33 mmol) in DCM (25 mL) was added diisopropylethylamine (3.57 mL, 20.83 mmol). To this solution was added (S)-5-(bis(2-(tert-butoxycarbonylamino)ethyl)amino)-2-(tert-butoxycarbonylamino)-5-oxopentanoic acid (XVI) (4.88 g, 9.16 mmol) and TBTU (2.94 g, 9.16 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was then diluted with DCM (50 mL) and washed with 2 N aqueous HCl, 1 N aqueous NaOH, brine, dried over MgSO4 and concentrated under vacuum to dryness. The residue was purified on a silica gel column using DCM:MeOH (100:1) to yield (12S,15R)-benzyl 12-(tert-butoxycarbonylamino)-8-(2-(tert-butoxycarbonylamino)ethyl)-2,2-dimethyl-4,9,13-trioxo-15-(4-(trifluoromethyl)benzyl)-3-oxa-5,8,14-triazahexadecan-16-oate (6.1 g, 7.28 mmol, 88% yield). 1H NMR (DMSO-d6) δ ppm 1.41 (s, 27H), 1.78-1.96 (m, 2H), 2.17 (brs, 1H), 2.59 (brs, 1H), 3.09-3.15 (m, 1H), 3.16-3.27 (m, 2H), 3.28-3.39 (m, 2H), 3.42-3.52 (m, 1H), 3.62 (brs, 1H), 4.06-4.14 (m, 1H), 4.83-4.91 (m, 1H), 5.08 (d, J=12 Hz, 1H), 5.17 (d, J=12 Hz, 1H), 5.76 (brs, 1H), 7.19 (d, J=8 Hz, 1H), 7.23-7.29 (m, 3H), 7.3-7.39 (m, 3H), 7.44 (d, J=8 Hz, 2H), 7.62 (brs, 1H); 19F NMR (DMSO-d6) δ ppm −61.84 (s, 3F); ESIMS found for C41H58F3N5O10 m/z 838.9 (M+H).

Provenance & Evidence