Methanol → 3-(4-(2-(4-Fluoro-3-(trifluoromethyl)benzamido)-2,2-bis(3-(trifluoromethoxy)phenyl)ethyl)phenyl)propanoic acid

Temperature

50 °C

To a solution of ethyl 3-(4-(2-(4-fluoro-3-(trifluoromethyl)benzamido)-2,2-bis(3-(trifluoromethoxy)phenyl)ethyl)phenyl)propanoate (11 mg, 0.015 mmol) in THF (0.75 mL) was added 1 N LiOH (0.15 mL) and methanol (0.30 mL). The reaction mixture was heated at 50° C. for 0.5 h. The solvents were removed under a stream of nitrogen then 1 N HCl (2 mL) was added to the residue and the mixture was extracted with CH2Cl2 (2×5 mL). The combined organics were dried over Na2SO4, filtered and the volatiles removed. The resulting residue was purified on ISCO silica gel eluting with 0 to 10% MeOH/CH2Cl2 to give 3-(4-(2-(4-fluoro-3-(trifluoromethyl)benzamido)-2,2-bis(3-(trifluoromethoxy)phenyl)ethyl)phenyl)propanoic acid (Example 277) as a clear, colorless oil (9 mg, 85% yield). LCMS: RT=2.18 min [M+H] 704.1 (2 min Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); NMR: 400 MHz 1H (CDCl3) δ ppm 2.55 (t, J=7.69 Hz, 2H), 2.82 (t, J=7.69 Hz, 2H), 3.83 (s, 2H), 6.54 (d, J=8.35 Hz, 2H), 6.60 (s, 1H), 6.93 (d, J=7.91 Hz, 2H), 6.97 (s, 2H), 7.08-7.14 (m, 4H), 7.17-7.23 (m, 1H), 7.28-7.33 (m, 2H), 7.73-7.77 (m, 1H), 7.83-7.86 (m, 1H).

1. customThe solvents were removed under a stream of nitrogen
2. addition1 N HCl (2 mL) was added to the residue
3. extractionthe mixture was extracted with CH2Cl2 (2×5 mL)
4. dry with materialThe combined organics were dried over Na2SO4
5. filtrationfiltered
6. customthe volatiles removed
7. customThe resulting residue was purified on ISCO silica gel eluting with 0 to 10% MeOH/CH2Cl2

ORD record

ord-d093b0075cb541f1aeef89d9d0b8b2d4

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08642576B2