Réaction #324530

Équation de réaction

3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoic acid

PyBOP

Azetidin-3-ol hydrochloride

DIPEA

→

1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol

Rendement 88.0%

Solvants

DMF

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGto stir an additional hour at room temperature
2. 2
   AutreThe mixture was then partitioned with ethyl acetate and 0.5 M aqueous sodium hydroxide solution
3. 3
   LavageThe organic layer was then washed with water (3×)
4. 4
   Séchagebrine and dried over anhydrous sodium sulfate
5. 5
   FiltrationFiltration and concentration

Mode opératoire

3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoic acid (2.1 g, 5.3 mmol) was taken into DMF (10 mL) followed by addition of PyBOP (2.6 g, 5.3 mmol) and the mixture was allowed to stir at room temperature over 15 minutes. Azetidin-3-ol hydrochloride (870 mg, 8.0 mmol) and DIPEA (1.85 mL, 11.2 mmol) was then added and the mixture was allowed to stir an additional hour at room temperature. The mixture was then partitioned with ethyl acetate and 0.5 M aqueous sodium hydroxide solution. The organic layer was then washed with water (3×) then brine and dried over anhydrous sodium sulfate. Filtration and concentration followed by silica gel flash chromatography using ethyl acetate:hexanes (5:1) eluent afforded 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol (2.09 g, 87% yield) as a colorless amorphous solid. 1H NMR (400 MHz, CDCl3): 8.47 (s, 1H), 7.39 (dd, 1H), 7.32 (d, 1H), 7.13-7.09 (m, 1H), 6.84-638 (m, 1H), 6.63-6.57 (m, 1H), 4.74-4.67 (m, 1H), 4.43-4.39 (m, 2H), 4.20-3.96 (br d, 2H), 2.50 (d, 1H).

Source