Sulfuric Acid → Methyl 5-amino-4-fluoro-1H-benzimidazole-6-carboxylate
Reaktionsgleichung
[NH2:1][C:2]1[C:11]([F:12])=[C:10]([NH2:13])[C:9]([NH2:14])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH:15](OCC)(OCC)OCC.OS(O)(=O)=O>C1COCC1>[CH3:7][O:6][C:4]([C:3]1[C:2]([NH2:1])=[C:11]([F:12])[C:10]2[N:13]=[CH:15][NH:14][C:9]=2[CH:8]=1)=[O:5]Komponenten
Edukt 3
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 1
Reaktionsbedingungen
- Temperatur
- 60 °C
Versuchsvorschrift
To a stirred solution of methyl 2,4,5-triamino-3-fluorobenzoate (9) (7.58 g, 38.1 mmol) in THF (152 mL, 20 vol) was added triethyl orthoformate (20.3 g, 22.8 mL, 137.0 mmol), followed by dropwise addition of H2SO4 (9.33 g, 18 M, 94.1 mmol). The mixture was then heated at 60° C. for 6 hours, at which point no starting material was detected by HPLC analysis. The solid product was filtered and rinsed with THF (150 mL, 20 vol), then transferred to a reaction vessel, suspended in water (150 mL) and the resulting mixture was neutralized to about pH 7.5 with 2 N NaOH. After stirring for 30 minutes, the suspension was filtered and the solid product was dried in a vacuum oven at 55° C., overnight to provide 6-amino-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester (12) 7.5 g, 94% yield (100% area by HPLC). 1H NMR (400 Hz, d6 DMSO) δ 3.53 (1H, br s, NH), 3.85, (3H, s, OMe), 6.10 (2H, br s, NH2), 7.90 (1H, s, Ar—H), 7.20 (1H, s, Ar—H). MS APCI (+) m/z 210 (M+1) detected with MS APCI (+).
Aufarbeitung
- filtrationThe solid product was filtered
- washrinsed with THF (150 mL, 20 vol)
- customtransferred to a reaction vessel
- filtrationthe suspension was filtered
- customthe solid product was dried in a vacuum oven at 55° C., overnight
Quellen und Nachweise
- ORD-Eintrag
- ord-e982a0cb2192494ea0e985ae875cca8a
- Quelldatensatz
- uspto-grants-2015_05
- Patentnummer
- US09024040B2
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