Introduction
This method is in demand due to a precursor availability on Chinese reagent market. Ethyl 3-oxo-4-phenylbutanoate CAS 718-08-1 is Phenylacetone (P2P, BMK) precursor, which allows to be turned into the target product pretty easy with a good literature yield 74% after column chromatography purification.
Equipment and glassware:
Equipment and glassware:
- Flask 10 ml;
- Laboratory scale (0.01-100 g is suitable);
- Ice/water bath;
- Magnetic stirrer with heating plate;
- Separatory funnel 250 ml;
- Beakers 100 x2, 50 x3;
- Pasteur Pipette;
- Glass rod and spatula;
Reagents:
- Ethyl 3-oxo-4-phenylbutanoate 0.412 g, 0.002 mol [CAS 718-08-1];
- PEG-400 (polyethylene glycol 400) 0.015 mL [CAS 25322-68-3];
- Sulfuric acid 1.5 mL 18 N 50%;
- Distilled water 20 ml;
- Dichloromethane (DCM) 45 ml;
- Anhydrous sodium sulphate Na2SO4;
P2P (Phenylacetone) Synthesis From Ethyl 3-oxo-4-phenylbutanoate
1. PEG-400 (polyethylene glycol 400) 0.015 mL is added to a stirred suspension of ethyl 3-oxo-4-phenylbutanoate 0.412 g, 0.002 mol in sulfuric acid 1.5 mL 18 N 50% in water in a pear shaped 10 ml flask with reflux condenser.
2. The reaction mixture is refluxed vigorously for 2–4 h.
3. Then, it was cooled to 0–5°С, diluted with ice-cold water 20 mL, and extracted with dichloromethane (DCM) 3 x 15 mL in a separatory funnel.
4. The combined organic layer is dried over anhydrous Na2SO4.
5. Next, the decanted extract is concentrated in vacuo to yield the crude phenylacetone (P2P; BMK) product.
Optional step
6. Silica-gel column chromatography (hexanes–EtOAc, 9:1) of the residue afforded Ethyl 3-oxo-4-phenylbutanoate in 74% yield.
Phenylacetone also can be steam distilled as described in the method.
2. The reaction mixture is refluxed vigorously for 2–4 h.
3. Then, it was cooled to 0–5°С, diluted with ice-cold water 20 mL, and extracted with dichloromethane (DCM) 3 x 15 mL in a separatory funnel.
4. The combined organic layer is dried over anhydrous Na2SO4.
5. Next, the decanted extract is concentrated in vacuo to yield the crude phenylacetone (P2P; BMK) product.
Optional step
6. Silica-gel column chromatography (hexanes–EtOAc, 9:1) of the residue afforded Ethyl 3-oxo-4-phenylbutanoate in 74% yield.
Phenylacetone also can be steam distilled as described in the method.
Source
- Prakash Rao, H. Surya, et al. "Novel synthesis of methyl ketones based on the Blaise reaction." Synthetic Communications® 39.10 (2009): 1825-1834. https://www.tandfonline.com/doi/abs/10.1080/00397910802594276
