Sodium hydride → 1,1-dimethylethyl {[1-[(4-chlorophenyl)methyl]-2-(1-methylethyl)-4,5,6,7-tetra hydro-1H-benzimidazol-7-yl]oxy}acetate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of Intermediate 58 (352 mg) in anhydrous N,N-dimethylformamide (15 mL) at 0° C. under an atmosphere of nitrogen was added sodium hydride (55 mg) 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 tert-butyl bromoacetate (0.18 mL) in one charge the reaction was stirred at 0° C. for a further 30 min before allowing to warm to ambient temperature over 1 hr. The reaction was stirred at ambient temperature for 3 hr. Sodium hydride (55 mg) as a 60% wt suspension on oil was added and the reaction stirred for 30 min. To the reaction was added tert-butyl bromoacetate (0.18 mL) in one charge. The reaction was quenched with water (75 mL) and extracted with ethyl acetate (75 mL). The extract was dried (hydrophobic frit) and concentrated in vacuo. The sample was loaded in dichloromethane and purified on silica using a 0-25% methanol-dichloromethane gradient. Separation poor all product containing fractions were combined and concentrated in vacuo. The sample was loaded in dichloromethane and purified on silica using a 0-100% ethyl acetate-cyclohexane gradient. The appropriate fractions were combined and concentrated in vacuo to give the title compound (130 mg). LC/MS MH+ 419, 421, Rt 1.00 min (2 min run). Chiral separation of this material using a chiralpak AD column eluting with 5% ethanol in heptane to provide the two enantiomers in order of elution:

Provenance & Evidence