3-(BENZYLOXY)-2-METHYL-4(1H)-PYRIDINONE

To a solution of 2 (13.8g, 0.064mol) in ethanol (25mL) was added ammonia solution (5OmL) and refluxed overnight. The solvent was removed under reduced pressure, then taken into water and adjusted to pH 1 with concentrated hydrochloric acid. The aqueous mixture was washed with ethyl acetate (3x) and the pH was adjusted to pH 10 with sodium hydroxide (2M.). The aqueous phase was extracted with chloroform (3?), dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure. Re-crystallisation from methanol/diethyl ether gave brown cubic crystals, mp 162-164°C. Yield 75percent. 1H NMR (CDCl3) ' 2.15 (3H, s, CH3), 5.03 (2H, s, CH2Ph), 6.35 (1?, d, J=6.9'z, 5-H), 7.25-7.31 (5?, m, CH2PA), 7.39 (IH, d, J=6.9Hz, 6-/2). C13H13NO2.To a solution of 2 (13.8 g, 0.064 mol) in ethanol (25 mL) was added ammonia solution (50 mL) and refluxed overnight. The solvent was removed under reduced pressure, then taken into water and adjusted to pH 1 with concentrated hydrochloric acid. The aqueous mixture was washed with ethyl acetate (3.x.) and the pH was adjusted to pH 10 with sodium hydroxide (2 M.). The aqueous phase was extracted with chloroform (3.x.), dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure. Re-crystallisation from methanol/diethyl ether gave brown cubic crystals, mp 162-164 °C. Yield 75percent. A clear solution of 3-(benzyloxy)-2-methyl-4H-pyran-4-one (150 g, 0.69 mol), ethanol (300 mL) and ammonium hydroxide (28.0-30.0percent solution, 690 mL, 10.5 mol) in a 2 L 3-necked round bottom flask equipped with a mechanical stirrer was heated to reflux for 5 h. 2) The compound 2 (162, 2g, 750mmol) was dissolved in ethanol (-187ml), and aqueous ammonia (28percent, 974ml) and a 6N aqueous sodium hydroxide solution (150ml, O00mmol) were added. After the reaction solution was stirred at 90 °C for 1 hour, this was cooled to under ice-cooling, and ammonium chloride (58g, 10S0mmol) was added, To the reaction solution was added chloroform, this was extracted, and the organic layer was washed with an aqueous saturated sodium bicarbonate solution, and dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, isopropyl alcohol and diethyl ether were added to the residue, and precipitated crystals were filtered to obtain 3-benzyloxy-2-methyl- 1H-pyridine-4-one 3 (69.1g, 43percent) as a pale yellow crystal.NMR (DMSO-dfi)δ: 2.05(3H, s), 5.04(2H, a), 6 14(1H, d, J=7 0Hz), 7, 31-7.42(5H, m), 7 46(1H, d, J=7.2Hz), 11.29(1H, brs).To a solution of 3-(benzyloxy)-2-methyl-4H-pyran-4-one (2.3 g) in acetonitirle (5 ml) was added aq.N in seal tube. The reaction mixture was heated at 80-90°C for 18 h. After completion of reaction, the reaction mixture was cooled at RT and diluted with ethyl acetate. The organic layer was separated and further aqueous layer was extracted with 10percent MeOH in DCM. The organic layer was concentrated to afford 2.3 g of desired product. 1H NMR (DMSO-dTriphenylphosphine (TPP) (2.9g, ll.16mm.ol, 1.2equiv.) was slowly added to a solution of 3 (2g, 9.30mmol) in dry tetrahydrofuran (2OmL), and the solution was cooled to 0°C in ice bath. Benzyl alcohol (1.2g, ll.l'mmol, 1.2equiv.) was later introduced dropwise followed by diethylazodicarboxylate (DEAD) (1.9g, ll.l6mmol, 1.2equiv.) in the same manner. After refluxing the reaction mixture overnight, the solvent was removed under reduced pressure and the residue was extracted with water. The mixture was adjusted to pH 1 with concentrated hydrochloric acid before washing with diethyl ether (4x). The pH of the aqueous fraction was increased to 8 with sodium hydroxide (2M.), followed by extraction with ethyl acetate (4x). The combined organic fractions were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give a white solid. Recrystallisation from chloroform/petroleum spirit gave white crystals, mp 85-87°C. Yield 79percent.vmax (KBr) 3264 (ring C-H), 1589, 1498, 1485 and 1449 (ring C=C), 1218 and 1066 (C-O-C) cm'1. 1H NMR (CDCl3) ' 2.43 (3H, s, CH3), 5.00 (2H, s, 3-OCH2Ph), 5.17 (2H, s, 4- OCH2Ph), 6.79 (1?, d, J=5.6'z, 5-H), 7.30-7.45 (10?, m, 3-OCH2PA and 4- OCH2PA), 8.13 (IH, d, J=5.6Hz, 6-H); mlz (FAB) 306 [(M+H)+]; HRMS (FAB): [(M+H)+], found 306.1504. C20H20NO2 requires 306.1494.Triphenylphosphine (TPP) (2.9 g, 11.16 mmol, 1.2 equiv) was slowly added to a solution of 3 (2 g, 9.30 mmol) in dry tetrahydrofuran (20 mL), and the solution was cooled to 0 °C in ice bath. Benzyl alcohol (1.2 g, 11.16 mmol, 1.2 equiv) was later introduced dropwise followed by diethylazodicarboxylate (DEAD) (1.9 g, 11.16 mmol, 1.2 equiv) in the same manner. After refluxing the reaction mixture overnight, the solvent was removed under reduced pressure and the residue was extracted with water. The mixture was adjusted to pH 1 with concentrated hydrochloric acid before washing with diethyl ether (4.x.). The pH of the aqueous fraction was increased to 8 with sodium hydroxide (2 M.), followed by extraction with ethyl acetate (4.x.). The combined organic fractions were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give a white solid. Recrystallisation from chloroform/petroleum spirit gave white crystals, mp 85-87 °C. Yield 79percent. numax (KBr) 3264 (ring C-H), 1589, 1498, 1485 and 1449 (ring CC), 1218 and 1066 (C-O-C) cm-1. 1H NMR (CDCl3) delta 2.43 (3H, s, CH3), 5.00 (2H, s, 3-OCH2Ph), 5.17 (2H, s, 4-OCH2Ph), 6.79 (1H, d, J = 5.6 Hz, 5-H), 7.30-7.45 (10H, m, 3-OCH2Ph and 4-OCH2Ph), 8.13 (1H, d, J = 5.6 Hz, 6-H); m/z (ESI): 290.8.The above white solid (7-propionyloxy-3-bromomethylcoumarin) (807.3 mg, 3 mmoL) was sequentially added to a 25 mL single-necked flask.2-methyl-3-benzyloxy-pyridine-4(1H)-one (430.5 mg, 2 mmol), Potassium carbonate (414.6 mg, 3 mmol), acetonitrile 12 mL, water 1.5 mL;The reflux reaction was heated until the end of the reaction by thin layer chromatography.The solvent was distilled off under reduced pressure.Column chromatography gave a yellow solid 7-1. The yield was 58%.General procedure: A mixture of 6 (239mg, 1.5mmol), 3a1 (139mg, 1.0mmol), anhydrous potassium carbonate (207mg, 1.5mmol), and acetonitrile (15mL) was refluxed for 6h, and the progress of the reaction was monitored by TLC (eluent: dichloromethane/methanol=15: 1 solvent mixture). The reaction mixture was concentrated under reduce pressure to afford yellow solid residue, which was purified by chromatography on silica gel to obtain the desired compound.

Molecular Weight:215.25
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:215.094628657
Monoisotopic Mass:215.094628657
Topological Polar Surface Area:38.3
Heavy Atom Count:16
Complexity:325
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes