6-Methoxy-4-chromanone

Representative procedure: 2, 3-dihydro-4H-chromen-4-one (7a). To the dioxalane 4a (1.20 g, 6.18 mmol) in an MeCN-H(2) Preparation Example 8 By the reaction and treatment in the same manner as in Preparation Example 5 using Step C The latter was added to 600 ml of hot, stirred polyphosphoric acid maintained at 75 C. and the mixture stirred for 2 hours. The temperature rose to a maximum of 89 C. over the first one-half hour, then fell to the 75 C. bath temperature. The reaction mixture was quenched into 3.2 liters of ice and water and extracted with 1.2 liters of ethyl acetate. The organic extract was in sequence with 600 ml each of H2 O, saturated NaHCO3 and saturated NaCl, dried over MgSO4 and stripped to 180 g of solids which were taken up in 400 ml CH2 Cl2, treated with activated carbon and restripped to a like quantity of solids. The latter were recrystallized from isopropyl ether to yield purified title product, 120 g, m.p. 46-48 C., identical with the commercial product.The latter was added to 600 ml of hot, stirred polyphosphoric acid maintained at 75 C. and the mixture stirred for 2 hours. The temperature rose to a maximum of 89 C. over the first one-half hour, then fell to the 75 C. bath temperature. The reaction mixture was quenched into 3.2 liters of ice and water and extracted with 1.2 liters of ethyl acetate. The organic extract was extracted in sequence with 600 ml each of H2 O, saturated NaHCO and saturated NaCl, dried over MgSO4 and stripped to 180 g of solids which were taken up in 400 ml CH2 Cl2, treated with activated carbon and restripped to a like quantity of solids. The latter were recrystallized from isopropyl ether to yield purified title product, 120 g, mp 46-48 C., identical with the commercial product.The latter was added to 600 ml of hot, stirred polyphosphoric acid maintained at 75 C. and the mixture stirred for 2 hours. The temperature rose to a maximum of 89 C. over the first one-half hour, then fell to the 75 C. bath temperature. The reaction mixture was quenched into 3.2 liters of ice and water and extracted with 1.2 liters of ethyl acetate. The organic extract was in sequence with 600 ml each of H2 O, saturated NaHCO3 and saturated NaCl, dried over MgSO4 and stripped to 180 g of solids which were taken up in 400 ml CH2 C2, treated with activated carbon and restripped to a like quantity of solids. The latter were recrystallized from isopropyl ether to yield purified title product, 120 g, m.p. 46-48 C., identical with the commercial product.General procedure: In a 50 mL flask, phenol (30 mmol) and acrylonitrile (33 mmol) were added to the flask, and then 1 mL triethylamine was added to the flask and stirred for 24 h under reflux. The reaction system was added with ethyl ether, then washed with NaOH aq. (20% wt.) and 2N HCl aq. and then dried with anhydrous sodium sulfate. Then the organic phase was concentrated under reduced pressure, and the resulting residue was added with about 40 mL conc. HCl and refluxed with several hours. The reaction system was extracted with ethyl acetate three times and then dried with anhydrous sodium sulfate. Then the organic phase was concentrated under reduced pressure without further purification. To the solution of carboxylic acid (10 mmol) in dry CH2Cl2 (50 mL) was added 0.2 mL of DMF at 0 C. Oxalyl chloride (15 mmol) was then added dropwise under nitrogen atmosphere at 0 C. The reacion was stirred at 0 C for 16 h and the mixture was concentrated at high vacuum to give the desired acid chloride, which was directly use without further purification. To the acid chloride in dry CH2Cl2 (50 mL) was added AlCl3 (15 mmol) slowly under a positive atmosphere of nitrogen 0 C. The mixture was stirred at 0 C overnight. The mixtures were quenched with water followed by extraction with CH2Cl2 . The combined organic layer was dried over anhydrous Na2SO4 , filtered and concentrated. The residue was purified by column chromatography to give corresponding ketone. A 50 mL oven-dried schlenk flask containing a magnetic stir bar was charged with sodium hydride (dry, 60%, 0.48 g, 2.0 equiv) and capped with a septum. The reaction flask was evacuated and backfilled with argon (this process was repeated a total of three times), and the flask was equipped with a balloon filled with argon. THF (10 mL) was added to the flask, and the mixture was cooled down to 0 C in an ice bath. Triethylphosphonoacetate (2.8 g, 2.5 mL, 2.0 equiv) was then added dropwise via syringe to the suspension of sodium hydride over 15 minutes, and the mixture was stirred for 30 min. The solution of corresponding ketone (6 mmol, 1.0 equiv) in THF (10 mL) was then added to the reaction flask via syringe at 0 C. The reaction mixture was allowed to warm to 60 C (detected by TLC analysis). The septum and the balloon were removed, and the reaction was carefully quenched by the slow addition of aqueous sat. NH4Cl solution. The mixture was then extracted with ethyl acetate (3×), washed with brine, dried with Na2SO4 , filtered, concentrated in vacuo and purified by silica gel chromatography to afford the corresponding alpha, beta-unsaturated ester.

Molecular Weight:178.18
XLogP3:1.3
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:178.062994177
Monoisotopic Mass:178.062994177
Topological Polar Surface Area:35.5
Heavy Atom Count:13
Complexity:202
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes