Diisopropylethylamine → 4-(2-Benzyloxycarbonylamino-3-methyl-butyryl)-3-phenoxy-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution containing Cbz-Val-OH (233 mg, 0.92 mmol) and crude 13 (256 mg, 0.84 mmol) in anhydrous NMP (3 mL) was cooled to 0° C. HATU (352 mg, 0.93 mmol) and DIPEA (125 mg, 1.01 mmol) were added and the reaction mixture was slowly warmed to ambient temperature. After 16 h, the reaction mixture was diluted with diethyl ether and EtOAc (1:4) and washed successively with 1M HCl, aqueous NaHCO3, water, and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by flash silica gel chromatography (4:1 hexanes/EtOAc) to afford 410 mg (90%) of 14 as a white solid. 1H NMR (CDCl3, 300 MHz), mixture of rotomers: δ7.31 (m, 9H), 6.96 (m, 1H), 5.79 (m, 1H). 5.07 (m, 2H), 4.91 (d, J=2.7 Hz, 1H), 4.51-4.43 (m, 2H), 4.35 (t, J=7.5 Hz, 1H), 4.07-3.99 (m, 2H), 3.90 (app d, J=26.4 Hz, 0.5H), 3.77 (app d, J=27.3 Hz, 0.5H), 3.31 (m, 2H), 2.49 (m, 0.5H), 2.35 (m, 0.5H), 1.92 (m, 1H), 1.51 (m, 9H), 0.95 (m, 6H) ppm.

Provenance & Evidence