Tetrahydrofuran → HCID 24993315, compound

Temperature

-78 °C

To a solution of 20 mg (0.07 mmol) of 3-[(3aR,4R,5S,7aS)-5-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}4-(4-fluorophenyl)octahydro-2H-isoindol-2-yl] cyclopent-2-en-1-one (Example 7) and 170 mg (0.39 mmol) MoOPH in ˜2 mL dry THF under nitrogen atmosphere at −78° C. was added ×x0.076 mL (0.15 mmol) of 2.0 M solution of KHMDS. The resulting mixture was stirred at −78° C. for 2hr then quenched by the addition of sat. aq. NH4Cl. The mixture was extracted with EtOAc. The combined organic extracts were washed with brine, dried over drying agent and filtered. The residue was purified by prep TLC eluting with CHCl3/2N NH3 in MeOH (9/1) to afford the title compound as a mixture of diastereomers. 1H-NMR (CDCl3): δ: 7.71 (1H, s), 7.23 (2H, s), 7.00 (2H, m), 6.93 (2H, t, J=8.2 Hz), 4.85, 4.71 (H, s), 4.47 (1H, m), 4.20 (1H, m), 3.80-3.65 (1H, m),3.37 (1H, m), 3.25-3.08 (1H, m), 3.10-2.80 (3H, m), 2.58 (1H, m), 2.50-2.30 (1H, m), 2.15 (1H, m), 1.95 (2H, m), 1.35 (3H, d, J=6.0 Hz). MS: (MH)+572.5. The diastereomers were separated by HPLC on CHIRACEL AS column eluting with hexanes/EtOH (85/15) to afford the individual diastereomers.

1. customthen quenched by the addition of sat. aq. NH4Cl
2. extractionThe mixture was extracted with EtOAc
3. washThe combined organic extracts were washed with brine
4. customdried
5. customover drying agent
6. filtrationfiltered
7. customThe residue was purified by prep TLC
8. washeluting with CHCl3/2N NH3 in MeOH (9/1)

ORD record

ord-428962b8e0e7430a9f84c2f76ec184b4

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07645790B2