Lithium Hexamethyldisilazide → (4R)-2-oxo-N-[(1R)-1-phenylpropyl]-4-(pyrimidin-2-ylsulfanylmethyl)azetidine-1-carboxamide

Beteiligte Stoffe

Reaktionsschritte

To a solution of 4(R)-(pyrimidin-2-ylsulfanyl-methyl)azetidin-2-one (61.5 mg, 0.315 mmol) in THF (3 mL) at 0° was added dropwise LiHMDS (1M/THF) (0.33 mL, 0.331 mmol). After the reaction mixture was stirred 15 min at 0°, then cooled to −78°, 1(R)-phenylpropyl isocyanate (example 1) (0.53M/toluene, 0.63 mL, 0.315 mmol) was added dropwise and the mixture was warmed to room temperature and stirred for 1.5 h. The reaction mixture was quenched with H2O and diluted with EtOAc. The organic phase was washed with H2O and brine, dried (MgSO4), filtered and evaporated. The product was purified by flash chromatography (SiO2, 30% EtOAc/hexane) to give 2-oxo-4(R)-(pyrimidin-2-ylsulfanylmethyl)azetidine-1-carboxylic acid (1(R)-phenylpropyl)amide (75 mg, 67% yield) as a viscous gum. 1H NMR (400 MHz, CDCl3) δ 8.45 (d, J=4.8 Hz, 2H), 7.29-7.17 (m, 5H), 6.94 (t, J=4.8 Hz, 1H), 6.82 (d, J=8.3 Hz, 1H) 4.71 (q, J=7.6 Hz, 1H), 4.33-4.28 (m, 1H), 4.03 (dd, J=14.2, 3.3 Hz, 1H), 3.39 (dd, J=14.2, 8.3 Hz, 1H), 3.03 (dd, J=16.0, 5.6 Hz, 1H), 2.89 (dd, J=16.0, 3.0 Hz, 1H), 1.83-1.75 (m, 2H), 0.86 (t, J=7.3 Hz, 3H); IR (neat) υ 1758, 1692 cm−1; FAB MS m/z 357.3 (MH+); HRMS calcd. for C18H21N4O2S (MH+) 357.1385, found 357.1379.

Herkunft & Nachweise