Methanol → HCID 178525566, Verbindung

Trifluoroacetic acid (44.6 mL, 583.0 mmol, 30.0 eq) is added at room temperature to a stirred solution of (trans-4-tert-butoxycarbonylamino-cyclohexyl)-acetic acid (5.0 g, 19.4 mmol, 1.0 eq) in dichloromethane (50 mL). After 3 hours stirring at room temperature, the reaction mixture is concentrated, the resulting residue is dissolved in pyridine (150 mL) and phthalic anhydride (5.0 g, 33.0 mmol, 1.7 eq) is added at room temperature. The reaction mixture is heated to reflux for 4 hours, pyridine is then removed and acetic anhydride (40 mL) is added. The resulting mixture is heated to reflux for 3 hours, then extracted with ethyl acetate (3×200 mL) and water (200 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by column chromatography (silica gel, eluent: dichloromethane:methanol, 50:1 to 10:1, v/v) to afford [trans-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-cyclohexyl]-acetic acid as a white solid (4.82 g, 86% yield).

1. concentrationthe reaction mixture is concentrated
2. dissolutionthe resulting residue is dissolved in pyridine (150 mL)
3. temperatureThe reaction mixture is heated
4. temperatureto reflux for 4 hours
5. custompyridine is then removed
6. additionacetic anhydride (40 mL) is added
7. temperatureThe resulting mixture is heated
8. temperatureto reflux for 3 hours
9. extractionextracted with ethyl acetate (3×200 mL) and water (200 mL)
10. dry with materialThe combined organic layers are dried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. customto give a residue that
14. customis purified by column chromatography (silica gel, eluent

ORD-Eintrag

ord-a6f30e8ed89e40f5861625ebd20d9311

Quelldatensatz

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08927541B2