반응 #67794

반응 방정식

lithium bis(trimethylsilyl)amide

Lithium bis(trimethylsilyl)amide

5-fluoro-2-phenylisonicotinic acid

2-fluoro-4-iodoaniline

→

5-[(2-fluoro-4-iodophenyl)amino]-2-phenylisonicotinic acid

수율 56.6%

용매

EtOAc

THF

THF

반응 조건

후처리

1. 1
   workup.STIRRINGthe mixture was stirred for 1 h
2. 2
   온도The mixture was warmed to room temperature
3. 3
   workup.STIRRINGstirred overnight
4. 4
   세척washed with dilute HCl (20 ml), water (20 ml)
5. 5
   기타dried
6. 6
   농축concentrated
7. 7
   기타Purified on Flashmaster

실험 절차

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)]

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