Methyl bromoacetate → (6R,7aS)-[6-(4-bromobenzyloxy)-2-(3,5-dichlorophenyl)-1,3-dioxo-tetrahydro-pyrrolo[1,2-c]imidazol-7a-yl]-acetic Acid Methyl Ester

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Reaction Conditions

Reaction Steps

The compound of formula (Io), wherein Z is methoxycarbonylmethyl and the bonds depicted as wavy bonds define the 7aS,6R stereoisomer, was prepared as follows. 1.65 mL of a solution of LDA (1 M) in THF (1.5 eq.) was added to a solution of (7aR,6R)-2-(3,5-dichloro-phenyl)-6-(4-bromobenzyloxy)-tetrahydro-pyrrolo[1,2-c]imidazole-1,3-dione (500 mg) (1.1 mmol) (Ex. 6) in 5 mL of dry THF cooled to −65° C. under nitrogen. The reaction mixture was stirred for 1 h then treated with a solution of methyl bromoacetate (340 mg) (2 eq.) in 3 mL of THF. After 1 h at −65° C., the reaction mixture was allowed to warm to −20° C., stirred for 2 h, and then poured in a mixture of water/EtOAc (1:1, 20 mL). The organic layer was washed with water, dried over MgSO4, and evaporated under reduced pressure. The resulting oily residue was purified over SiO2 column (25 g) (eluent: EtOAc/cyclohexane 3/7) to afford the above-titled compound (28.8 mg) as a foam. NMR (CDCl3, 200 MHz): 7.43 (2H, d), 7.35 (1H, m), 7.15-7.0 (4H, m), 4.4-4.2 (3H, dd+m), 4.15 (1H, m), 3.7 (3H, s), 3.2-3.0 (2H, dd+d), 2.75 (1H, d), 2.52 (1H, dd), 2.05 (1H, dd).

Provenance & Evidence