Diisopropylethylamine → 9H-fluoren-9-ylmethyl {2-[(4-{[(tert-butoxycarbonyl)amino]methyl}phenyl)amino]-2-oxoethyl}carbamate

Temperature

0 °C

To a solution of Fmoc-Glycine (16 g, 54 mmol, 1.0 eq.) in dry DMF (160 mL) at 0° C. was added N,N-diisopropylethylamine (14 g, 108 mmol, 2.0 eq) and N N,N′,N′-Tetramethyl-O-(benzotriazol-1-yl)uronium tetrafluoroborate (16 g, 54 mmol, 1.0 eq). The mixture was stirred at 0° C. for 30 min and a solution of tert-butyl [4-(glycylamino)benzyl]carbamate (12 g, 54 mmol, 1.0 eq.) in dry DMF (50 mL) was added. The mixture was stirred at room temperature overnight poured into ice water (400 mL) and extracted with EtOAc (400 mL×2). The organic layer was washed with brine (200 mL×2), dried over Na2SO4 and concentrated in vacuum. The residue was re-crystallized from EtOAc (200 mL) and petroleum ether (400 mL) to afford #B118 (18 g, 66.6%) as a white solid. 1H NMR (400 Hz, DMSO-d6): δ 9.93 (s, 1H), 7.91 (d, 2H), 7.75 (d, 2H), 7.61 (m, 1H), 7.52 (d, 2H), 7.43 (m, 2H), 7.36 (m, 3H), 7.18 (d, 3H), 4.32 (d, 2H), 4.26 (m, 1H), 4.07 (d, 2H), 3.80 (d, 2H), 1.39 (s, 9H)

1. stirringThe mixture was stirred at room temperature overnight
2. extractionextracted with EtOAc (400 mL×2)
3. washThe organic layer was washed with brine (200 mL×2)
4. dry with materialdried over Na2SO4
5. concentrationconcentrated in vacuum
6. customThe residue was re-crystallized from EtOAc (200 mL) and petroleum ether (400 mL)
7. customto afford #B118 (18 g, 66.6%) as a white solid

ORD record

ord-c8b3a153a0b54dc0960b8e7dd14fc917

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09169264B2