Benzoic acid, 3-methoxy-4-propoxy-, methyl ester synthesis
- Product Name:Benzoic acid, 3-methoxy-4-propoxy-, methyl ester
- CAS Number:3535-26-0
- Molecular formula:C12H16O4
- Molecular Weight:224.25
Yield:3535-26-0 98%
Reaction Conditions:
Stage #1: 4-hydroxy-3-methoxybenzoic acid methyl esterwith Cs2CO3 in N,N-dimethyl-formamide at 20; for 0.0833333 h;
Stage #2: propyl bromide in N,N-dimethyl-formamide at 100; for 16 h;
Steps:
Synthesis of methyl 4-cyclobutoxy-3-methoxybenzoate (10)
General procedure: A vial was charged with methyl vanillate (8) (200 mg, 1.1 mmol), cesium carbonate (540mg, 1.65 mmol) and DMF (1.1 mL). The resulting suspension was stirred for 5 minutesat room temperature before the dropwise addition of bromocyclobutane (160 μL, 1.65mmol). The reaction was then heated to 100 °C for 16 hours. LCMS showed completeconsumption of the starting material. The reaction was diluted with the addition of waterand DCM, and the layers were separated. The aqueous layer was extracted with DCM x3, and the combined organic material was passed through a phase separator,concentrated onto silica gel, and purified by flash column chromatography (ISCO (silicagel column, hexanes : EtOAc; 0-10% EtOAc gradient). The desired product was isolated as a colorless oil (200 mg, 77% yield).
References:
Reed, Carson W.;Rodriguez, Alice L.;Kalbfleisch, Jacob J.;Seto, Mabel;Jenkins, Matthew T.;Blobaum, Anna L.;Chang, Sichen;Lindsley, Craig W.;Niswender, Colleen M. [Bioorganic and Medicinal Chemistry Letters,2022,vol. 74,art. no. 128923] Location in patent:supporting information
