2-Fluoro-4-iodoaniline → 5-[(2-Fluoro-4-iodophenyl)amino]-2-phenylisonicotinic acid

HRID 218884Notes

Reaction equation

C[Si]([N-][Si](C)(C)C)(C)C.[Li+].F[C:12]1[C:17]([C:18]([OH:20])=[O:19])=[CH:16][C:15]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[N:14][CH:13]=1.[F:27][C:28]1[CH:34]=[C:33]([I:35])[CH:32]=[CH:31][C:29]=1[NH2:30]>C1COCC1.CCOC(C)=O>[F:27][C:28]1[CH:34]=[C:33]([I:35])[CH:32]=[CH:31][C:29]=1[NH:30][C:12]1[C:17]([C:18]([OH:20])=[O:19])=[CH:16][C:15]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[N:14][CH:13]=1

Participants

Conditions

Temperature: -78 °C

Procedure

Lithium bis(trimethylsilyl)amide (2.8 ml, 1.0 M in THF, 2.76 mmol) was added to a suspension of 5-fluoro-2-phenylisonicotinic acid (500 mg, 2.30 mmol) in THF (10 ml) at −78° C. The dark colored suspension was stirred for 30 min. In another flask, 2-fluoro-4-iodoaniline (709.30 mg, 2.99 mmol, 1.30 eq) was dissolved in (15 ml) THF and cooled to −78° C. To this solution lithium bis(trimethylsilyl)amide (5 ml, 1.00 M, 5.06 mmol, 2.20 eq) was added and the mixture was stirred for 1 h. The reaction mixture became very viscous. To this, the homogeneous solution of acid-LiHMDS mixture was added via syringe. The mixture was warmed to room temperature and stirred overnight. Diluted with EtOAc (300 ml), washed with dilute HCl (20 ml), water (20 ml), and then dried and concentrated. Purified on Flashmaster using 100 g cartridge to obtain 565 mg of 5-[(2-fluoro-4-iodophenyl)amino]-2-phenylisonicotinic acid. LC/MS: [8.59 min; 435 (M+1)]

Workup

stirringthe mixture was stirred for 1 h
temperatureThe mixture was warmed to room temperature
stirringstirred overnight
washwashed with dilute HCl (20 ml), water (20 ml)
customdried
concentrationconcentrated
customPurified on Flashmaster

Sources & evidence

ORD record: ord-38cdc947e29f4634807d18bde57e9f12
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08198457B2

Reaction notes

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