119736-16-2

Basic information

• Product Name: 3-(Benzyloxy)-4-oxo-4h-pyran-2-carboxylic acid
• Synonyms: 3-(Benzyloxy)-4-oxo-4h-pyran-2-carboxylic acid;4-oxo-3-((phenylmethyl)oxy)-4h-pyran-2-carboxylic acid;4-Oxo-3-(phenylmethoxy)-4H-pyran-2-carboxylic acid
• CAS NO: 119736-16-2
• Molecular Formula: C₁₃H₁₀O₅
• Molecular Weight: 246.2155
• EINECS: -0
• Mol File: 119736-16-2.mol
• Article Data: 29

Chemical Properties

• Boiling Point: 487.5±45.0 °C(Predicted)
• Appearance: /
• Density: 1.39±0.1 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• PKA: 2.00±0.20(Predicted)
• CAS DataBase Reference: 3-(Benzyloxy)-4-oxo-4h-pyran-2-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 3-(Benzyloxy)-4-oxo-4h-pyran-2-carboxylic acid(119736-16-2)
• EPA Substance Registry System: 3-(Benzyloxy)-4-oxo-4h-pyran-2-carboxylic acid(119736-16-2)

Safety Data

• Hazardous Substances Data: 119736-16-2(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 119736-16-2 differently. You can refer to the following data:
1. There are a variety of preclinical, clinical, and marketed new drugs that contain 3-(benzyloxy)-4-oxo-4H-pyran-2-carboxylic acid fragments. As shown in the figure below, several types of drug molecules, as well as the marketed drugs such as dulutevir (GSK1349572) and baloxavir (Baloxavir) contain this important structural fragment.
2. 4-Oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic Acid is an intermediate in the synthesis of Dolutegravir (D528800), a second generation HIV-1 integrase strand transfer inhibitor.

Synthesis

Add 2-(hydroxymethyl)-3-(benzyloxy)-4H-pyran-4-one (Compound IV) 39.8Kg, dichloromethane (340L) and water (170L) to the reaction kettle to start stirring. Then add sodium bicarbonate (77Kg), sodium bromide (1.6Kg) and 2,2,6,6-tetramethylpiperidine-nitrogen-oxide (TEMPO) (2.3Kg), cool to 5℃, drop Add 10% sodium hypochlorite (340Kg). After the dropwise addition, stir at 5°C for 1 hour. The reaction is completed. Add 30% aqueous sodium thiosulfate solution (242L) and stir for 1 h. Add concentrated hydrochloric acid to adjust pH=4, separate the organic phase, extract the aqueous phase twice with dichloromethane (120L), combine the organic phases, and concentrate under reduced pressure to obtain the crude product. The crude product was recrystallized from acetonitrile to obtain 3-(benzyloxy)-4-oxo-4H-pyran-2-carboxylic acid (Compound VI) 32.4Kg, purity 99%, yield 77%. LC-MS: [M+H] + = 247.06, [M] + = 245.05; 1 H NMR (DMSO-d 6 ) δ8.00 (d, J = 5.6 Hz, 1H), 7.17 (s, 5H), 6.34 (d, J = 5.7 Hz, 1H), 4.91 (s, 2H), 2.30 (s, 1H).

Synthetic route

3-(benzyloxy)-4-oxo-4H-pyran-2-carbaldehyde (500371-01-7) → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
With sodium hypochlorite; aminosulfonic acid In water; acetone at 20℃; for 2h;	97%
With sodium chlorite; aminosulfonic acid In water; acetone at 20℃; Cooling with ice;	88%
With sodium chlorite; aminosulfonic acid In water; acetone at 20℃; Cooling;	86%

2-(hydroxymethyl)-3-(phenylmethoxy)-4H-pyran-4-one (119736-15-1) → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
With palladium on activated charcoal; oxygen; sodium hydroxide In water at 60℃; under 7600.51 Torr; Autoclave; Green chemistry;	92%
With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; sodium bromide In dichloromethane; water at 5℃; for 1h; Solvent; Reagent/catalyst; Temperature; Large scale;	83%
With jones reagent	19%

C16H17NO3 → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
With sodium periodate In water	83.5%
Stage #1: C16H17NO3 With sodium periodate; water In N,N-dimethyl-formamide at 25℃; for 0.5h; Stage #2: With sodium chlorite; aminosulfonic acid; water In N,N-dimethyl-formamide; acetone at 25℃; for 1h;	82%
Multi-step reaction with 2 steps 1: sodium periodate / water; acetone / 5.27 h / 20 °C / Inert atmosphere; Cooling with ice 2: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; sodium hypochlorite / water; acetonitrile / 2.63 h / 20 °C / Inert atmosphere; Cooling with ice View Scheme

3-O-benzylmaltol (61049-69-2) → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
With chromium(VI) oxide; periodic acid In acetonitrile at 20℃; for 1.5h;	71%
Multi-step reaction with 2 steps 1: SeO2 / various solvent(s) / 155 °C 2: NaClO2; NH2SO3H / acetone; H2O View Scheme
Multi-step reaction with 2 steps 1: SeO2 / various solvent(s) / 12 h / 160 °C 2: NaClO2; aq. H2O2; NaH2PO4 / acetonitrile / 1 h / 20 °C View Scheme

C20H16O3 (1229006-11-4) → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
Stage #1: C20H16O3 With sodium periodate; sulfuric acid; rhodium(III) chloride hydrate In water; acetonitrile at 20℃; for 3.5h; Stage #2: With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate In ethyl acetate at 25℃; for 1.5h; Product distribution / selectivity;	70%
Stage #1: C20H16O3 With sodium periodate; rhodium(III) chloride hydrate; sulfuric acid In water; acetonitrile at 20℃; for 3.5h; Stage #2: With sodium chlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate In water; acetonitrile at 25℃; for 1.5h; Reagent/catalyst;	70%
Stage #1: C20H16O3 With ruthenium trichloride; sodium periodate Stage #2: With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical	70%

2-[(E)-2-phenylethenyl]-3-[(phenylmethyl)oxy]-4H-pyran-4-one (1206102-05-7) → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
Stage #1: 2-[(E)-2-phenylethenyl]-3-[(phenylmethyl)oxy]-4H-pyran-4-one With sodium periodate; rhodium(III) chloride hydrate; water In ethyl acetate; acetonitrile at 25℃; for 1h; Stage #2: With sodium chlorite In ethyl acetate; acetonitrile at 25℃; for 1h;	56%
Stage #1: 2-[(E)-2-phenylethenyl]-3-[(phenylmethyl)oxy]-4H-pyran-4-one With sodium periodate; rhodium(III) chloride hydrate In water; ethyl acetate; acetonitrile at 25℃; for 1h; Stage #2: With sodium chlorite In water; ethyl acetate; acetonitrile at 25℃; for 1h;	56%
Stage #1: 2-[(E)-2-phenylethenyl]-3-[(phenylmethyl)oxy]-4H-pyran-4-one With ruthenium trichloride; sodium periodate In water; ethyl acetate; acetonitrile at 15℃; for 2h; Inert atmosphere; Stage #2: With sodium chlorite In water; ethyl acetate; acetonitrile at 20℃; for 2h;	52%
Multi-step reaction with 2 steps 1: ruthenium trichloride; sodium periodate; sulfuric acid / acetonitrile; water / 20 °C / Large scale 2: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; sodium hypochlorite / acetonitrile; water; ethyl acetate / 20 °C / Large scale View Scheme

Maltol (118-71-8) → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 83 percent / aq. NaOH / methanol / 75 °C 2: SeO2 / various solvent(s) / 155 °C 3: NaClO2; NH2SO3H / acetone; H2O View Scheme
Multi-step reaction with 3 steps 1: sodium hydroxide / methanol / 8 h / Reflux 2: selenium(IV) oxide / 14 h / 159 °C 3: sodium hypochlorite; aminosulfonic acid / water; acetone / 2 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: potassium carbonate / acetonitrile / Inert atmosphere; Reflux; Large scale 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 3 h / -60 °C / Inert atmosphere 2.2: 2 h / -60 °C / Inert atmosphere 3.1: triethylamine; methanesulfonyl chloride / dichloromethane / 2 h / -30 °C / Inert atmosphere 3.2: 0.33 h / 0 °C 4.1: ruthenium trichloride; sodium periodate / acetonitrile; ethyl acetate; water / 2 h / 15 °C / Inert atmosphere 4.2: 2 h / 20 °C View Scheme

benzyl bromide (100-39-0) + ZnCr-benzoate*3H2O → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 83 percent / aq. NaOH / methanol / 75 °C 2: SeO2 / various solvent(s) / 155 °C 3: NaClO2; NH2SO3H / acetone; H2O View Scheme

benzyl chloride (100-44-7) → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide / methanol / 8 h / Reflux 2: selenium(IV) oxide / 14 h / 159 °C 3: sodium hypochlorite; aminosulfonic acid / water; acetone / 2 h / 20 °C View Scheme
Multi-step reaction with 2 steps 2: aminosulfonic acid; sodium hypochlorite View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / methanol / 1 h / Reflux 2: periodic acid; chromium(VI) oxide / acetonitrile / 1.5 h / 20 °C View Scheme

benzyl bromide (100-39-0) → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium carbonate / acetonitrile / Inert atmosphere; Reflux; Large scale 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 3 h / -60 °C / Inert atmosphere 2.2: 2 h / -60 °C / Inert atmosphere 3.1: triethylamine; methanesulfonyl chloride / dichloromethane / 2 h / -30 °C / Inert atmosphere 3.2: 0.33 h / 0 °C 4.1: ruthenium trichloride; sodium periodate / acetonitrile; ethyl acetate; water / 2 h / 15 °C / Inert atmosphere 4.2: 2 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: potassium carbonate / acetonitrile / 5 h / 80 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 2 h / -60 °C 2.2: 1 h / -60 °C 3.1: triethylamine; methanesulfonyl chloride / tetrahydrofuran / 30 °C 3.2: 0.5 h / 30 °C 4.1: sodium periodate; rhodium(III) chloride hydrate; water / acetonitrile; ethyl acetate / 1 h / 25 °C 4.2: 1 h / 25 °C View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate / acetonitrile / 5 h / 13 - 80 °C / Large scale 2: bromobenzene; selenium(IV) oxide / 13 h / 140 °C / Dean-Stark 3: sodium chlorite; aminosulfonic acid / water; acetone / 0.67 h / 20 °C / Cooling with ice View Scheme

2-(2-hydroxy-2-phenylethyl)-3-[(phenylmethyl)oxy]-4H-pyran-4-one (1206102-04-6) → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triethylamine; methanesulfonyl chloride / dichloromethane / 2 h / -30 °C / Inert atmosphere 1.2: 0.33 h / 0 °C 2.1: ruthenium trichloride; sodium periodate / acetonitrile; ethyl acetate; water / 2 h / 15 °C / Inert atmosphere 2.2: 2 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: triethylamine; methanesulfonyl chloride / tetrahydrofuran / 30 °C 1.2: 0.5 h / 30 °C 2.1: sodium periodate; rhodium(III) chloride hydrate; water / acetonitrile; ethyl acetate / 1 h / 25 °C 2.2: 1 h / 25 °C View Scheme
Multi-step reaction with 2 steps 1.1: triethylamine; methanesulfonyl chloride; 1,8-diazabicyclo[5.4.0]undec-7-ene / tetrahydrofuran; 1-methyl-pyrrolidin-2-one / 0.5 h / 30 °C 2.1: rhodium(III) chloride hydrate; sodium periodate; sulfuric acid / water; acetonitrile / 3.5 h / 20 °C 2.2: 1.5 h / 25 °C View Scheme

C21H20O6S → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / tetrahydrofuran; 1-methyl-pyrrolidin-2-one / 0.5 h / 30 °C 2.1: sodium periodate / rhodium(III) chloride hydrate / water; ethyl acetate; acetonitrile / 1 h / 25 °C 2.2: 1 h / 25 °C View Scheme
Multi-step reaction with 2 steps 1: 1,8-diazabicyclo[5.4.0]undec-7-ene 2: ruthenium trichloride; sodium periodate View Scheme

3-hydroxy-pyran-4-one (496-63-9) → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydroxide / water; methanol / 1 h / 5 °C / Large scale 1.2: 24 h / 5 - 20 °C / Large scale 2.1: sodium hydroxide / water; methanol / 3 h / 70 °C / Large scale 3.1: sodium hydrogencarbonate; sodium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hypochlorite / water; dichloromethane / 1 h / 5 °C / Large scale View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydroxide / water; methanol / 1 h / 5 °C / Large scale 1.2: 24 h / 5 - 20 °C / Large scale 2.1: potassium carbonate / methanol / 2 h / 70 °C / Large scale 3.1: sodium hydrogencarbonate; sodium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hypochlorite / water; dichloromethane / 1 h / 5 °C / Large scale View Scheme

(2-furyl)methyl alcohol (98-00-0) → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium acetate; chlorine / ethanol; water / 5 °C / Large scale 2.1: sodium hydroxide / water; methanol / 1 h / 5 °C / Large scale 2.2: 24 h / 5 - 20 °C / Large scale 3.1: sodium hydroxide / water; methanol / 3 h / 70 °C / Large scale 4.1: sodium hydrogencarbonate; sodium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hypochlorite / water; dichloromethane / 1 h / 5 °C / Large scale View Scheme
Multi-step reaction with 4 steps 1.1: sodium acetate; chlorine / ethanol; water / 5 °C / Large scale 2.1: sodium hydroxide / water; methanol / 1 h / 5 °C / Large scale 2.2: 24 h / 5 - 20 °C / Large scale 3.1: potassium carbonate / methanol / 2 h / 70 °C / Large scale 4.1: sodium hydrogencarbonate; sodium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hypochlorite / water; dichloromethane / 1 h / 5 °C / Large scale View Scheme

2-Hydroxymethyl-3-hydroxy-pyran-4(1H)-one (1968-51-0) → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / water; methanol / 3 h / 70 °C / Large scale 2: sodium hydrogencarbonate; sodium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hypochlorite / water; dichloromethane / 1 h / 5 °C / Large scale View Scheme
Multi-step reaction with 3 steps 1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; potassium bromide; sodium hypochlorite / dichloromethane; water / 0.5 h / 0 - 10 °C / Large scale 2: sodium hydroxide / water; methanol / 4 h / 25 - 55 °C / Large scale 3: sodium hydroxide / water; methanol / 4 h / 30 °C View Scheme
Multi-step reaction with 3 steps 1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; potassium bromide; sodium hypochlorite / dichloromethane; water / 0.5 h / 0 - 10 °C / Large scale 2: potassium hydroxide / water; methanol / 4 h / 25 - 55 °C 3: sodium hydroxide / water; methanol / 4 h / 30 °C View Scheme
Multi-step reaction with 3 steps 1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; potassium bromide; sodium hypochlorite / dichloromethane; water / 0.5 h / 0 - 10 °C / Large scale 2: potassium carbonate / water; ethanol / 4 h / 25 - 55 °C 3: sodium hydroxide / water; methanol / 4 h / 30 °C View Scheme

2-methyl-4-oxo-4H-pyran-3-yl acetate (28787-36-2) → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / 1,2-dichloro-ethane / 7 h / 60 °C / Green chemistry 2.1: sodium hydroxide / water / 2 h / Reflux; Green chemistry 2.2: 3 h / Reflux; Green chemistry 3.1: sodium hydroxide; palladium on activated charcoal; oxygen / water / 60 °C / 7600.51 Torr / Autoclave; Green chemistry View Scheme

3-hydroxy-4-oxo-4H-pyran-2-carboxylic acid → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / water; methanol / 4 h / 25 - 55 °C / Large scale 2: sodium hydroxide / water; methanol / 4 h / 30 °C View Scheme
Multi-step reaction with 2 steps 1: potassium hydroxide / water; methanol / 4 h / 25 - 55 °C 2: sodium hydroxide / water; methanol / 4 h / 30 °C View Scheme

C20H16O5 → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
With sodium hydroxide In methanol; water at 30℃; for 4h; Temperature; Reagent/catalyst;	6.9 g

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
With hydrogenchloride; water at 100℃; for 5h; Reagent/catalyst; Temperature;	10.9 g

benzyl alcohol (100-51-6) → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium t-butanolate / tetrahydrofuran / 1 h / 10 - 20 °C / Cooling with ice 1.2: 20 °C 2.1: 1 h / 50 - 60 °C 3.1: sodium t-butanolate / tetrahydrofuran / 2.17 h / 0 - 30 °C / Inert atmosphere; Cooling with ice 4.1: hydrogenchloride; water / 5 h / 100 °C View Scheme

4-benzyloxy-3-oxobutyric acid methyl ester (82961-76-0) → 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1 h / 50 - 60 °C 2: sodium t-butanolate / tetrahydrofuran / 2.17 h / 0 - 30 °C / Inert atmosphere; Cooling with ice 3: hydrogenchloride; water / 5 h / 100 °C View Scheme

(R)-1-pyrrolidin-2-ylmethylcarbamic acid tert-butyl ester (719999-54-9) + 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) → C23H28N2O6 (1309561-94-1)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran for 16h;	100%

4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) → 3-(benzyloxy)-4-oxo-1,4-dihydropyridine-2-carboxylic acid hydrochloride (1246617-42-4)

Conditions	Yield
With ammonium hydroxide at 20℃; for 12h;	100%
Stage #1: 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid With ammonia In water at 20℃; for 12h; Stage #2: With hydrogenchloride In water
Stage #1: 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid With ammonium hydroxide at 20℃; Stage #2: With hydrogenchloride In water

4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) → 3-(benzyloxy)-4-oxo-1,4-dihydropyridine-2-carboxylic acid

Conditions	Yield
With ammonia In water at 20℃; for 12h;	100%
With ammonium hydroxide In water at 20℃; for 16h;
With ammonium hydroxide In water at 20℃; for 16h;
With ammonium hydroxide In water at 20℃; for 16h;
With ammonium hydroxide In water at 25℃;

4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) + ethyl iodide (75-03-6) → ethyl 3-(benzyloxy)-4-oxo-4H- pyran-2-formate (1332855-94-3)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 20℃;	100%
With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-d6-formamide at 20℃;	100%
With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 20℃;	100%

2,2,2-trifluoroethanol (75-89-8) + 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) → C15H11F3O5

Conditions	Yield
Stage #1: 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 5h; Cooling with ice; Stage #2: 2,2,2-trifluoroethanol With dmap; triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice;	100%
Stage #1: 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 5h; Stage #2: 2,2,2-trifluoroethanol With dmap; triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice;	100%

4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) + dimethyl sulfate (77-78-1) → 3-benzyloxy-4-oxo-4H-pyran-2-carboxylic acid methyl ester

Conditions	Yield
Stage #1: 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid With potassium carbonate In acetone at 20℃; Stage #2: dimethyl sulfate In acetone at 20 - 55℃; Temperature;	98%
With sodium hydrogencarbonate In N,N-dimethyl-formamide at 20℃; for 14.5h;	94%
With sodium hydrogencarbonate In N,N-dimethyl acetamide at 25℃; for 7h;

4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) + 2-(2-Aminoethoxy)ethanol (929-06-6) → C17H19NO6

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide for 24h;	94.71%

4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) + methyl iodide (74-88-4) → 3-benzyloxy-4-oxo-4H-pyran-2-carboxylic acid methyl ester

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 20℃; Cooling with ice;	90%
With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 20℃; for 10h;	89%
With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 20℃; for 20h;	69%
With sodium hydrogencarbonate In 1-methyl-pyrrolidin-2-one for 16h; Heating;

4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) → C13H11NO5

Conditions	Yield
With hydroxylamine hydrochloride In methanol; water for 10h; Reflux;	90%

4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) + methylamine (74-89-5) → 3-(benzyloxy)-N-methyl-4-oxo-4H-pyran-2-carboxamide

Conditions	Yield
Stage #1: 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid With 1-hydroxy-pyrrolidine-2,5-dione; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃; for 5.5h; Stage #2: methylamine In tetrahydrofuran at 20℃;	86%

3-Amino-1,2-propanediol (616-30-8, 13552-31-3) + 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) → 1-(2,3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1,4-dihydro-2-pyridinecarboxylic acid (1206102-06-8)

Conditions	Yield
In ethanol for 1h; Reflux;	85%
In ethanol at 65 - 80℃; for 8.5h; Product distribution / selectivity;	83%
With pyridine In ethanol at 65 - 80℃; for 8.5h;	83%

ethanamine hydrochloride (557-66-4) + 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) → C15H15NO4

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 1h;	80%

C11H22N2O2*ClH + 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) → C24H30N2O6

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 2h;	78%

C33H63N7O9 + 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) → C72H87N7O21

Conditions	Yield
With dmap; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃;	34%

4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) + diazomethyl-trimethyl-silane (18107-18-1) → 3-benzyloxy-4-oxo-4H-pyran-2-carboxylic acid methyl ester

Conditions	Yield
With methanol at 20℃;
In tetrahydrofuran; methanol; hexane at 20℃; for 1.5h; Cooling with ice;

1-hydroxy-pyrrolidine-2,5-dione (6066-82-6) + 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) → 3-benzyloxy-4-oxo-4H-pyran-2-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester (1037293-71-2)

Conditions	Yield
Stage #1: 1-hydroxy-pyrrolidine-2,5-dione; 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid In tetrahydrofuran at 20℃; for 0.5h; Stage #2: With dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃; for 3h;
With dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃; for 3.5h;
With dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃; for 5h;

4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) → TRENMAN (880763-30-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: tetrahydrofuran / 0.5 h / 20 °C 1.2: DCC / tetrahydrofuran / 3 h / 20 °C 2.1: 2.7 g / tetrahydrofuran / 20 °C 3.1: aq. HCl; AcOH / 24 h / 20 °C View Scheme

4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) → N,N',N''-(nitrilotris(ethane-2,1-diyl))tris(3-(benzyloxy)-4-oxo-4H-pyran-2-carboxamide) (880763-29-1)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: tetrahydrofuran / 0.5 h / 20 °C 1.2: DCC / tetrahydrofuran / 3 h / 20 °C 2.1: 2.7 g / tetrahydrofuran / 20 °C View Scheme
Multi-step reaction with 2 steps 1: dicyclohexyl-carbodiimide / tetrahydrofuran / 3.5 h / 20 °C 2: tetrahydrofuran / 20 °C View Scheme

4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) → 3-hydroxy-4-oxo-4H-pyran-2-carboxylic acid methyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: MeOH / 20 °C 2: aq. HCl / 6 h / Heating View Scheme

4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) → 3-hydroxy-4-oxo-4H-pyran-2-carboxylic acid

Conditions	Yield
Multi-step reaction with 3 steps 1: MeOH / 20 °C 2: aq. HCl / 6 h / Heating 3: NaOH / methanol / 20 °C View Scheme

benzyl bromide (100-39-0) + 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) → 3-benzyloxy-5-bromo-4-oxo-4H-pyrane-2-carboxylic acid methyl ester (500371-73-3)

Conditions	Yield
Stage #1: 4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid; diazomethyl-trimethyl-silane In tetrahydrofuran; methanol; hexane at 0 - 20℃; for 1.5h; Stage #2: With bromine In chloroform at 75℃; for 48h; Stage #3: benzyl bromide With potassium carbonate In DMF (N,N-dimethyl-formamide) at 80℃;

4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid (119736-16-2) → 3-(benzyloxy)-4-oxo-4H-pyran-2-carbonyl chloride (845724-16-5)

Conditions	Yield
With oxalyl dichloride; N,N-dimethyl-formamide In chloroform at 20℃; for 0.5h;
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane for 0.5h;
With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 5h; Cooling with ice;

Upstream product

• 119736-15-1 2-(hydroxymethyl)-3-(phenylmethoxy)-4H-pyran-4-one 
• 1229006-11-4 C₂₀H₁₆O₃ 
• 1206102-05-7 2-[(E)-2-phenylethenyl]-3-[(phenylmethyl)oxy]-4H-pyran-4-one 
• 100-44-7 benzyl chloride 
• 100-39-0 benzyl bromide 
• 1206102-04-6 2-(2-hydroxy-2-phenylethyl)-3-[(phenylmethyl)oxy]-4H-pyran-4-one 
• 1246616-66-9 dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate 
• 100-51-6 benzyl alcohol 
• 82961-76-0 4-benzyloxy-3-oxobutyric acid methyl ester 
• 28787-36-2 2-methyl-4-oxo-4H-pyran-3-yl acetate 
• 1968-51-0 2-Hydroxymethyl-3-hydroxy-pyran-4(1H)-one 
• 98-00-0 (2-furyl)methyl alcohol 
• 496-63-9 3-hydroxy-pyran-4-one 
• 61049-69-2 3-O-benzylmaltol 

Downstream Products

• 1037293-71-2 3-benzyloxy-4-oxo-4H-pyran-2-carboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester 
• 880763-29-1 N,N',N''-(nitrilotris(ethane-2,1-diyl))tris(3-(benzyloxy)-4-oxo-4H-pyran-2-carboxamide) 
• 500371-73-3 3-benzyloxy-5-bromo-4-oxo-4H-pyrane-2-carboxylic acid methyl ester 
• 845724-20-1 3-benzyloxy-4-oxo-4H-pyran-2-carboxylic acid 4-fluorobenzylamide 
• 1206102-06-8 1-(2,3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1,4-dihydro-2-pyridinecarboxylic acid 
• 1229006-18-1 1-[2,2-bis(methyloxy)ethyl]-4-oxo-3-[(phenylmethyl)oxy]-1,4-dihydro-2-pyridine carboxylic acid 
• 1229006-31-8 C₁₆H₁₅NO₄ 
• 1332855-93-2 C₂₄H₁₈FNO₅S 
• 1402887-82-4 N,N',N''-(nitrilotris(ethane-2,1-diyl))tris(3-(benzyloxy)-4-oxo-1,4-dihydropyridine-2-carboxamide) 
• 1206102-07-9 1-(2,3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1,4-dihydro-2-pyridinecarboxylic acid methyl ester 
• 1206102-08-0 methyl 1-(2,2-dihydroxyethyl)-4-oxo-3-[(phenylmethyl)oxy]-1,4-dihydro-2-pyridinecarboxylate 

Relevant articles and documents

Purification and characterization of molybdenum-containing aldehyde dehydrogenase that oxidizes benzyl maltol derivative from Pseudomonas nitroreducens SB32154

Maltol derivatives are used in a variety of fields due to their metal-chelating abilities. In the previous study, it was found that cytochrome P450 monooxygenase, P450nov, which has the ability to effectively convert the 2-methyl group in a maltol derivative, transformed 3-benzyloxy-2-methyl-4-pyrone (BMAL) to 2-(hydroxymethyl)-3-(phenylmethoxy)-4H-pyran-4-one (BMAL-OH) and slightly to 3-benzyloxy-4-oxo-4 H-pyran-2-carboxaldehyde (BMAL-CHO). We isolated Pseudomonas nitroreducens SB32154 with the ability to convert BMAL-CHO to BMAL-COOH from soil. The enzyme responsible for aldehyde oxidation, a BMAL-CHO dehydrogenase, was purified from P. nitroreducens SB32154 and characterized. The purified BMAL-CHO dehydrogenase was found to be a xanthine oxidase family enzyme with unique structure of heterodimer composed of 75 and 15 kDa subunits containing a molybdenum cofactor and [Fe-S] clusters, respectively. The enzyme showed broad substrate specificity toward benzaldehyde derivatives. Furthermore, one-pot conversion of BMAL to BMAL-COOH via BMAL-CHO by the combination of the BMAL-CHO dehydrogenase with P450nov was achieved.

Synthesis method of 3-(benzyloxy)-4-oxo-4H-pyran-2-carboxylic acid

The invention discloses a synthesis method of 3-(benzyloxy)-4-oxo-4H-pyran-2-carboxylic acid. The synthesis method sequentially comprises the following steps: S1, condensing 4-chloroacetoacetate and benzyl alcohol to obtain an intermediate I; S2, condensing the intermediate I with N,N-dimethylformamide dimethyl acetal to obtain an intermediate II; S3, performing ring closing on the intermediate IIand oxalic acid diester to obtain an intermediate III; and S4, decarboxylating the intermediate III in an acidic aqueous solution to obtain a target product. The method has the advantages of simple steps, mild conditions, cheap and easily available raw materials, and reduction of the cost of a target patent medicine.

Preparation method of pyrone compound

The invention provides a preparation method of a pyrone compound, and belongs to the field of pharmaceutical chemicals. According to the method, a pyrone compound sequentially reacts with acetal, concentrated sulfuric acid and sodium chlorite respectively, and extraction is performed to obtain a high-purity pyrone compound. The product produced by the method has the characteristics of high purity,high yield, low cost, simple operation and stable process.