Dimethylformamide → 5-(2-{tert-Butoxycarbonyl-[2-(3-chloro-phenyl)-2-hydroxy-ethyl]-amino}-propyl)-benzo[1,3]dioxole-2,2-dicarboxylic acid bis-methoxycarbonyl-methyl ester

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 5-(2-{tert-butoxycarbonyl-[2-(3-chloro-phenyl)-2-hydroxy-ethyl]-amino}-propyl)-benzo[1,3]dioxole-2,2-dicarboxylic acid (500 mg, 0.96 mmol) and DMF (10 mL) was added K2CO3 (132 mg, 0.96 mmol) and methyl-2-bromoacetate (0.23 mL, 366 mg, 2.40 mmol). After stirring at 50° C. for 4 h, the reaction mixture was cooled to 23° C., quenched with 5 mL sat. aq. NaHCO3, and extracted with 3×30 mL of EtOAc. The combined organics were washed with 2×50 mL brine, dried over MgSO4, filtered and concentrated to a yellow oil. Flash chromatography on silica gel, eluting with hexane/EtOAc (4/1 to 2/1), gave 508 mg (79%) of product as a colorless oil; 1H NMR (300 MHz, CDCl3): δ 1.22 (d, J=6.9 Hz, 3H), 1.41 (brs, 9H), 2.50-2.60 (brm, 1H), 2.60-2.75 (brm, 1H), 3.06-3.15 (brm, 1H), 3.45-3.60 (brm, 1H), 3.76 (s, 3H), 3.77 (s, 3H), 4.05-4.20 (brm, 1H), 4.70-4.79 (brm, 1H), 4.79(s, 2H), 4.80(s, 2H), 5.42-5.51 (brs, 1H), 6.60-6.91 (complexm, 4H), 7.20-7.43(complexm, 3H); MS (ES) m/z (relative intensity): 666 (M+, (100), 610 (25).

Provenance & Evidence