Reaktion #434086

Reaktionsgleichung

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

3-acetamido-phthalic anhydride

sodium acetate

→

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

Ausbeute 45.0%

Lösungsmittel

acetic acid

Reaktionsbedingungen

Vorschrift

3-(4-Acetylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy -phenyl)-propionic acid was prepared by the procedure of Example 4 from 3-amino-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid (2.7g, 13 mmol), 3-acetamido-phthalic anhydride (4.0 g, 14.5 mmol) and sodium acetate (1.2 g, 14.5 mmol) in acetic acid (50 ml) to give 3-(4-acetylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid (2.6 g, 45%) as yellowish solid. mp 89–91° C.; 1HNMR (CDCl3): δ 1.42 (t, J=7.5 Hz, 3H, OCH2CH3), 2.51 (s, 3H, CH3CO), 3.19 (dd, J=5.8, 15.5 Hz, 1H, CH2), 3.79 (dd, J=8.4, 15.5 Hz, 1H, CH2), 4.08 (q, J=7.5 Hz, 2H, OCH2CH3), 5.65–5.71 (m, 1H, CHN), 6.52 (t, JH-F=75 Hz, 1H, CF2H), 7.03–7.11 (m, 3H, Ar), 7.45 (d, J=7.5 Hz, 1H, Ar), 7.63 (t, J=7.5 Hz, 1H, Ar), 8.72 (d, J=8.3 Hz, 1H, Ar), 9.46 (s, 1H, NHCO). 13C NMR (CDCl3): δ 14.6, 24.8, 35.6, 50.3, 64.7, 98.4, 99.1, 111.8, 113.5, 115.2, 115.9, 118.2, 120.1, 120.2, 122.7, 125.0, 131.0, 136.0, 136.5, 137.4, 138.1, 140.0, 140.1, 140.2, 150.6, 167.4, 169.5, 169.7, 175.1; Anal. Calcd. for C22H20F2N2O7 +0.17 H2O: C, 56.77; H, 4.40; N, 6.06; H2O 0.66. Found: C, 56.60; H, 4.43; N, 6.02, H2O, 0.66.

Quelle