Isopropanol → tert-Butyl (4-{(1S,2R)-1-[(4-fluorophenyl)amino]-2-({[2-(4-methoxyphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]methyl}thio)-3-oxo-3-[(4S)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]propyl}phenoxy)acetate

Participants

Reaction Conditions

Reaction Steps

Tetraisopropyl orthotitanate (0.31 ml, 1.06 mmol) was added to a solution of TiCl4 (1M in CH2Cl2, 3.18 ml, 3.18 mmol) in CH2Cl2 (50 ml) at 0° C. under inert atmosphere. The mixture was stirred for ten minutes. (4S)-3-[({[2-(4-Methoxyphenyl)-5,5-dimethyl-1,3-dioxan-2-yl]methyl}thio)acetyl]-4-phenyl-1,3-oxazolidin-2-one (2.00 g, 4.24 mmol) in dry CH2Cl2 (50 ml) was added dropwise over 20 minutes. The mixture was stirred for ten minutes. tert-Butyl (4-{[(4-fluorophenyl)imino]methyl}phenoxy)acetate (2.79 g, 8.48 mmol) in dry CH2Cl2 (50 ml) was added dropwise over 30 minutes. The mixture was cooled to −30° C. and stirred for 20 minutes. Ethyl diisopropyl amine (1.45 ml, 8.48 mmol) in 10 ml dry CH2Cl2 was added dropwise over ten minutes and the mixture was stirred at −30° C. for five hours. The mixture was cooled to −78° C. Isopropanol (60 ml) was added and the temperature was allowed to rise overnight. H2O (100 ml) was added and the mixture was stirred for 20 minutes and extracted twice with diethyl ether. The combined organic layers were washed with water, dried (MgSO4) and concentrated under reduced pressure. Purification by flash-chromatography (hexane:EtOAc 3:1) afforded 2.00 g (59%) of the title compound as a yellow solid. 1H-NMR (CDCl3, 200 MHz): δ 0.6 (s, 3H), 1.3 (s, 3H), 1.5 (s, 9H), 2.6-2.9 (m, 2H), 3.3-3.5 (m, 4H), 3.8 (s, 3H), 4.1-4.3 (m, 2H), 4.5 (s, 2H), 4.6-4.8 (m, 2H), 5.0-5.4 (s, broad, 1H), 5.4 (m, 1H), 5.7 (d, 1H), 6.4 (m, 2H), 6.6-6.8 (m, 4H), 6.8-7.0 (m, 4H), 7.1-7.4 (m, 7H).

Provenance & Evidence