تفاعل #155433

معادلة التفاعل

(S)-(1-(chlorocarbonyl)pyrrolidin-2-yl)methyl acetate

2,6-difluoro-4-hydroxybenzaldehyde

triethylamine

CH2Cl2

→

(S)-3,5-difluoro-4-formylphenyl 2-(acetoxymethyl)pyrrolidine-1-carboxylate

المردود 50.1%

المذيبات

water

ظروف التفاعل

المعالجة

1. 1
   أخرىTo a 250 mL dry round bottom flask
2. 2
   أخرىThe CH2Cl2 layer was separated
3. 3
   استخلاصthe aqueous layer was extracted continually with CH2Cl2 (80 mL×2)
4. 4
   تجفيفThe combined CH2Cl2 solution was dried over Na2SO4
5. 5
   أخرىAfter removal of the solvent
6. 6
   أخرىthe residue was purified with a silica gel chromatography (heptane/ethyl acetate, gradient eluting)

الإجراء التجريبي

To a 250 mL dry round bottom flask were added (S)-(1-(chlorocarbonyl)pyrrolidin-2-yl)methyl acetate (6.79 g, 33.0 mmol), 2,6-difluoro-4-hydroxybenzaldehyde (4.74 g, 30 mmol), triethylamine (5.40 mL, 39.0 mmol) and anhydrous CH2Cl2 (40 mL). The resulting mixture was stirred at room temperature for 2 days, then water (80 mL) was added to the reaction mixture. The CH2Cl2 layer was separated, and the aqueous layer was extracted continually with CH2Cl2 (80 mL×2). The combined CH2Cl2 solution was dried over Na2SO4. After removal of the solvent, the residue was purified with a silica gel chromatography (heptane/ethyl acetate, gradient eluting) to give (S)-3,5-difluoro-4-formylphenyl 2-(acetoxymethyl)pyrrolidine-1-carboxylate (4.92 g) as a colorless oil. Yield: 46%. 1H NMR (CDCl3, 300 MHz, mixture of two isomers): δ=10.28 (s, 1H), 6.97 (t, J=11.4 Hz, 2H), 4.33-4.12 (m, 3H), 3.65-3.55 (m, 2H), 2.10-2.01 (m, 7H). 13C NMR (CDCl3, 75.5 MHz, mixture of two isomers): δ=183.5, 170.7 (d, J=7.3 Hz), 163.6 (dd, J=262.5, 8.6 Hz), 157.0, 150.8 (d, J=14.6 Hz), 112.6, 106.2 (d, J=25.0 Hz), 64.4, 63.8, 56.8, 56.4, 47.4, 47.3, 28.7, 27.8, 23.8, 22.9, 20.8.

المصدر