Ethyl Acetate → Ethyl [3-[(4-chlorophenyl)methyl]-4-hydroxy-2-(1-methylethyl)-3,4,5,6,7,8-hexahydrocyclohepta[d]imidazol-4-yl]acetate

Temperature

-78 °C

Ethyl acetate (1.08 mL) in 2-methylTHF (1 ml) was added dropwise to a stirred solution of LiHMDS, 1M in THF (11.1 mL) cooled to −78° C. under nitrogen atm. The mixture was stirred at −78° C. under nitrogen for 30 mins. Then Intermediate 3 (700 mg) in 2-methylTHF (5 ml) was added dropwise. The RM was stirred at −78° C. under nitrogen for 4 hours. An excess of sat NH4Cl aq. sol. was added and the resulting suspension was warmed up to room temp and extracted with EtOAc (100 ml). The phases were separated and the aqueous layer was again extracted with EtOAc (50 ml), the phases were separated. The organics were combined, dried (hydrophobic frit) and concentrated under vacuum. The residue was purified on silica (100 g) using a dichloromethane:ethyl acetate 0-100% gradient. The desired fractions were combined and concentrated under vacuum to give the title compound (670 mg) LC/MS MH+ 405, Rt 0.89 min (2 minute run).

1. stirringThe RM was stirred at −78° C. under nitrogen for 4 hours
2. temperaturethe resulting suspension was warmed up to room temp
3. extractionextracted with EtOAc (100 ml)
4. customThe phases were separated
5. extractionthe aqueous layer was again extracted with EtOAc (50 ml)
6. customthe phases were separated
7. customdried (hydrophobic frit)
8. concentrationconcentrated under vacuum
9. customThe residue was purified on silica (100 g)
10. concentrationconcentrated under vacuum

ORD record

ord-cc478918052e4e678074ada580313b3b

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399444B2