(S)-tert-Butyl 2-(5-(((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)-2-oxopyridin-1(2H)-yl)acetate → (S)-2-(5-(((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)-2-oxopyridin-1(2H)-yl)acetic Acid

HRID 2370854Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([C@H:13]([NH:21][C:22]([C:24]2[CH:25]=[CH:26][C:27](=[O:38])[N:28]([CH2:30][C:31]([O:33]C(C)(C)C)=[O:32])[CH:29]=2)=[O:23])[C:14]2[C:19]([F:20])=[CH:18][CH:17]=[CH:16][N:15]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]([F:12])([F:11])[F:10]>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C@H:13]([NH:21][C:22]([C:24]2[CH:25]=[CH:26][C:27](=[O:38])[N:28]([CH2:30][C:31]([OH:33])=[O:32])[CH:29]=2)=[O:23])[C:14]2[C:19]([F:20])=[CH:18][CH:17]=[CH:16][N:15]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]([F:11])([F:12])[F:10]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of (S)-tert-butyl 2-(5-(((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)carbamoyl)-2-oxopyridin-1(2H)-yl)acetate (633 mg, 1.173 mmol) and silica gel 60 (70.5 mg, 1.173 mmol) in toluene (10 mL) was heated to 110° C. After 3 h, the reaction was cooled to 23° C. and filtered. The residue was washed with 10% MeOH/DCM (100 mL), and the filtrates were combined and concentrated affording the title compound as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.08 (d, J=7.8 Hz, 1H), 8.44 (br. s., 2H), 7.87-8.02 (m, 1H), 7.76 (s, 1H), 7.42-7.63 (m, 3H), 7.34 (d, J=8.4 Hz, 1H), 6.66 (d, J=7.4 Hz, 1H), 6.41 (d, J=9.6 Hz, 1H), 4.57 (d, J=3.7 Hz, 2H). MS (ESI, positive ion) m/z: 484.1 (M+H).

Workup

temperaturethe reaction was cooled to 23° C.
filtrationfiltered
washThe residue was washed with 10% MeOH/DCM (100 mL)
concentrationconcentrated

Sources & evidence

ORD record: ord-2dcf2cee2e0f4bf393525bb50f51a509
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08710043B2

Reaction notes

Loading…