Ethyl bromoacetate → Ethyl {[3-[(3,4-dichlorophenyl)methyl]-2-(1-methylethyl)-3,4,5,6,7,8-hexahydrocyclohepta[d]imidazol-4-yl]oxy}acetate

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To a stirred solution of Intermediate 8 (300 mg) in anhydrous Tetrahydrofuran (THF) (3 mL) at 0° C. under an atmosphere of nitrogen was added sodium hydride (102 mg, 2.55 mmol) as a 60% by weight suspension on mineral oil in one charge. The reaction was stirred at 0° C. for 30 min. To the reaction was added neat ethyl bromoacetate (0.284 mL) in one charge the reaction was then gradually allowed to warm to ambient temperature under an atmosphere of nitrogen over 20 hours. LCMS (high pH) showed a mixture of DP:SM (1:1). The reaction mixture was partitioned between EtOAc (50 ml) and sat NH4Cl aq sol (30 ml). The two phases were separated and the aqueous phase was extracted again with EtOAc (30 ml). The phases were separated, the organic extracts were combined, dried (hydrophobic frit) and concentrated under vacuum. The residue was by column chromatography on silica using a Cyclohexane:Ethyl acetate 0-100% gradient+Ethyl acetate:Methanol 0-20% gradient. The desired fractions were combined and concentrated under vacuum to give the desired product, 220 mg, yellow oil. LC/MS MH+ 439/441, Rt 3.37 mins (5 min run, high pH).

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