反応 #324530

反応方程式

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

収率 88.0%

溶媒

DMF

反応条件

後処理

1. 1
   workup.STIRRINGto stir an additional hour at room temperature
2. 2
   その他The mixture was then partitioned with ethyl acetate and 0.5 M aqueous sodium hydroxide solution
3. 3
   洗浄The organic layer was then washed with water (3×)
4. 4
   乾燥brine and dried over anhydrous sodium sulfate
5. 5
   ろ過Filtration and concentration

実験手順

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).

出典