Sodium Chloride → (1-{[(2-chloro-4-pyrimidinyl)oxy]methyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate

Participants

Reaction Steps

To a solution of 0.106 g (0.05 mmol) of (1-{[(2-chloro-4-pyrimidinyl)oxy]methyl}cyclobutyl)methanol in 2 mL of dichloromethane cooled to 0° C. was added a 1.0 M solution of 0.937 mL (0.75 mmol) of phosgene in toluene and the contents stirred for 16 h. The reaction mixture was concentrated and the residue was dissolved in 4 mL of tetrahydrofuran and added to a 0° C. solution of 0.132 g (0.50 mmol) of (3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamide and 0.259 mL (1.5 mmol) of N,N-diisopropylethylamine in 2 mL of tetrahydrofuran. After stirring for 5 h, ethyl acetate and saturated sodium chloride were added. The organic phase was isolated, dried using magnesium sulfate, concentrated under vacuum, and the residue was purified by silica gel chromatography eluting with ethyl acetate:hexane (7:3) to afford 0.215 g (89%) of (1-{[(2-chloro-4-pyrimidinyl)oxy]methyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 8.29 (d, J=6 Hz, 1H), 7.32-7.10 (m, 6H), 6.67 (d, J=6 Hz, 1H), 5.61-5.53 (m, 1H), 5.13-5.08 (m, 1H), 4.79, 4.89 (2d, J=5, 6 Hz, 1H), 4.36, 4.39 (2s, 2H), 4.38-4.18 (m, 3H), 3.84 (m, 1H), 2.07-1.50 (m, 10 H), 1.47-1.26 (m, 5H), 0.88 (m, 3H). LC-MS m/z 519 (M+H).

Provenance & Evidence