Sodium Iodide → Ethyl[3-[(4-chlorophenyl)methyl]-2-(1,1-dimethylethyl)-3,4,5,6,7,8-hexahydrocyclohepta[d]imidazol-4-yl]acetate

A mixture of TMSCl (0.513 mL), sodium iodide (601 mg) and acetonitrile (9 ml) was added to a stirred suspension of Intermediate 15 (420 mg) in acetonitrile (3 ml). The RM was stirred at room temp under nitrogen overnight. The reaction mixture was partitioned between EtOAc (50 ml) and sat. NaHCO3 aq. sol.: water (1:1, 50 ml). The two phases were separated and the aqueous phase was extracted again with EtOAc (50 ml). The phases were separated; the organic extracts were combined, dried (hydrophobic frit) and concentrated under vacuum. The residue was purified by reverse phase chromatography using an acetonitrile—0.1% NH3:water—with an amonium carbonate buffer modifier (pH=10) 5%-35% gradient. The desired fractions were combined and concentrated under vacuum. The mixture was purified by MDAP (Method B). The desired fractions were combined and concentrated under nitrogen blowdown to give the title compound (22 mg). LC/MS MH+ 403 Rt 1.09 min (2 minute run).

1. customThe reaction mixture was partitioned between EtOAc (50 ml) and sat. NaHCO3 aq. sol.
2. customThe two phases were separated
3. extractionthe aqueous phase was extracted again with EtOAc (50 ml)
4. customThe phases were separated
5. customdried (hydrophobic frit)
6. concentrationconcentrated under vacuum
7. customThe residue was purified by reverse phase chromatography
8. concentrationconcentrated under vacuum
9. customThe mixture was purified by MDAP (Method B)
10. concentrationconcentrated under nitrogen

ORDレコード

ord-e82b9fa59ff14eb893bdfa95ef0ccfb7

出典データセット

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08399444B2