Reaction #324530

Reaction equation

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

Yield 88.0%

Solvents

DMF

Conditions

Workup

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

Procedure

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