Cesium carbonate → 5-(2-(4-fluoro-2-methoxyphenoxy)-4-(perfluoroethyl)benzamido)picolinic Acid

HRID 1484171Notes

Reaction equation

F[C:2]1[CH:21]=[C:20]([C:22]([F:28])([F:27])[C:23]([F:26])([F:25])[F:24])[CH:19]=[CH:18][C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]([O:15]CC)=[O:14])=[N:11][CH:12]=1)=[O:5].[F:29][C:30]1[CH:35]=[CH:34][C:33]([OH:36])=[C:32]([O:37][CH3:38])[CH:31]=1.C([O-])([O-])=O.[Cs+].[Cs+].[OH-].[Na+]>CN1C(=O)CCC1.CO>[F:29][C:30]1[CH:35]=[CH:34][C:33]([O:36][C:2]2[CH:21]=[C:20]([C:22]([F:28])([F:27])[C:23]([F:24])([F:26])[F:25])[CH:19]=[CH:18][C:3]=2[C:4]([NH:6][C:7]2[CH:8]=[CH:9][C:10]([C:13]([OH:15])=[O:14])=[N:11][CH:12]=2)=[O:5])=[C:32]([O:37][CH3:38])[CH:31]=1

Participants

Conditions

Temperature: 40 °C

Procedure

Ethyl 5-[[2-fluoro-4-(1,1,2,2,2-pentafluoroethyl)benzoyl]amino]pyridine-2-carboxylate (40.63 mg, 0.10 mmol), 4-fluoro-2-methoxyphenol (42.64 mg, 0.30 mmol) and Cs2CO3 (97.75 mg, 0.30 mmol) in NMP (0.4 mL) was stirred at 90° C. for 1 hour. Aqueous 3M NaOH (100 μL) and MeOH (0.2 mL) were added and the mixture was stirred at 40° C. for 1 h. The mixture was diluted with methanol, filtered and purified by reverse phase HPLC using a gradient of ACN in Water (1-99%) and HCl as a modifier to give 5-(2-(4-fluoro-2-methoxyphenoxy)-4-(perfluoroethyl)benzamido)picolinic acid (72) (20.42 mg, 36%). ESI-MS m/z calc. 500.08. found 501.3 (M+1)+; Retention time: 1.69 minutes (3 minutes run). 1H NMR (400 MHz, DMSO) δ 11.08 (s, 1H), 8.95 (d, J=2.4 Hz, 1H), 8.33 (dd, J=8.6, 2.5 Hz, 1H), 8.08 (d, J=8.6 Hz, 1H), 7.90 (d, J=8.0 Hz, 1H), 7.54 (d, J=8.0 Hz, 1H), 7.31 (dd, J=8.8, 5.9 Hz, 1H), 7.16 (dd, J=10.7, 2.9 Hz, 1H), 6.98-6.85 (m, 1H), 6.80 (s, 1H), 3.72 (s, 3H) ppm.

Workup

filtrationfiltered
custompurified by reverse phase HPLC

Sources & evidence

ORD record: ord-878a91b523e643c5ad3dd260daad9907
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09421196B2

Reaction notes

Loading…