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 ×0.076 mL (0.15 mmol) of 2.0 M solution of KHMDS. The resulting mixture was stirred at −78° C. for 2 hr 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 (1 H, s), 7.23 (2 H, s), 7.00 (2 H, m), 6.93 (2 H, t, J=8.2 Hz), 4.85, 4.71 (1 H, s), 4.47 (1 H, m), 4.20 (1 H, m), 3.80-3.65 (1 H, m), 3.37 (1 H, m), 3.25-3.08 (1 H, m), 3.10-2.80 (3 H, m), 2.58 (1 H, m), 2.50-2.30 (1 H, m), 2.15 (1 H, m), 1.95 (2 H, m), 1.35 (3 H, 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-1188ac3b360e40839bb7701501b79926

Source dataset

uspto-grants-2008_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07345083B2