Diisopropylamine → 2-(4-Bromo-2-fluoro-benzyl)-3-tert-butoxycarbonylamino-propionic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of diisopropyl amine (1.3 mL, 9.0 mmol) in THF (20 mL) was added n-BuLi (1.6 M solution in hexanes, 5.6 mL, 9.0 mmol) at 0° C. The reaction was stirred at 0° C. for 15 minutes and then cooled to −78° C. A solution of 3-tert-butoxycarbonylamino-propionic acid tert-butyl ester (1.0 g, 4.1 mmol) in THF (5 mL) was added dropwise. The mixture was stirred at −78° C. for 2 hours. A solution of 4-Bromo-1-bromomethyl-2-fluoro-benzene (1.3 g, 4.9 mmol) in THF (4 mL) was added dropwise. After completion, the dry-ice bath was removed and the reaction was warmed to 0° C. in an ice bath. After stirring at 0° C. for 30 minutes, the reaction was poured into saturated NH4Cl aqueous solution. The organic layer was separated. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried and concentrated. The residue was purified by column chromatography (hexane:EtOAc, 20:1 to 5:1) to give 2-(4-Bromo-2-fluoro-benzyl)-3-tert-butoxycarbonylamino-propionic acid tert-butyl ester (1.35 g, 77%) as a colorless oil. 1H NMR (CDCl3, 400 MHz) δ 7.20 (d, J=8.0 Hz, 2H), 7.08 (t, J=8.0 Hz, 1H), 4.86 (m, 1H), 3.28 (m, 2H), 2.92 (m, 3H), 1.43 (s, 9H), 1.36 (s, 9H).

Provenance & Evidence