Reaktion #434066

Reaktionsgleichung

3-amino-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid

3-acetamido-phthalic anhydride

sodium acetate

→

3-(4-acetylamino-1,3-dioxo-1,3-dihydro -isoindol-2-yl)-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid

Ausbeute 147.4%

Lösungsmittel

acetic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture was heated
2. 2
   Temperaturat reflux temperature overnight
3. 3
   SonstigeThe solvent was removed in vacuo
4. 4
   ExtraktionThe resulted oil was extracted with ethyl acetate (50 ml) and water (30 ml)
5. 5
   WaschenThe organic layer was washed with water (30 ml×4), brine (30 ml)
6. 6
   Trocknendried over magnesium sulfate
7. 7
   SonstigeThe solvent was removed in vacuo
8. 8
   FiltrationThe suspension was filtered

Vorschrift

To a solution of 3-amino-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid (500 mg, 1.0 mmol) in acetic acid (10 ml) was added 3-acetamido-phthalic anhydride (390 mg, 1.9 mmol) and sodium acetate (160 mg, 1.9 mmol). The mixture was heated at reflux temperature overnight. The solvent was removed in vacuo. The resulted oil was extracted with ethyl acetate (50 ml) and water (30 ml). The organic layer was washed with water (30 ml×4), brine (30 ml) and dried over magnesium sulfate. The solvent was removed in vacuo and the resulted oil was slurried with ether for 2 hours. The suspension was filtered to give 3-(4-acetylamino-1,3-dioxo-1,3-dihydro -isoindol-2-yl)-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid as a white solid (720 mg, 85%). 1HNMR (CDCl3): δ 0.35–0.39 (m, 2H), 0.64–0.68 (m, 2H), 1.15–1.36 (m, 1H), 2.27 (s, 3H), 3.24 (dd, J=5.8, 17 Hz, 1H), 3.82 (dd, J=10, 17 Hz, 1H), 3.88 (d, J=8.3 Hz, 2H), 5.70 (dd, J=5.8, 10 Hz, 1H), 6.59 (t, JH-F=75 Hz, 1H), 7.06–7.14 (m, 3H), 7.48 (d, J=7.3 Hz, 1H), 7.65 (t, J=7.5 Hz, 1H), 8.76 (d, J=8.3 Hz, 1H), 9.47 (s, 1H).

Quelle