1246616-66-9

Basic information

• Product Name: diMethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-
• Synonyms: diMethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-;4-Oxo-3-(phenylMethoxy)-4H-pyran-2,5-dicarboxylic acid 2,5-diMethyl ester;Dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate;Dolutegravir Intermediate3;Dolutegravir DL4B
• CAS NO: 1246616-66-9
• Molecular Formula: C₁₆H₁₄O₇
• Molecular Weight: 318.27816
• Product Categories: Dolutegravir INTERMEDIATES
• Mol File: 1246616-66-9.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 534.9±50.0 °C(Predicted)
• Appearance: /
• Density: 1.34±0.1 g/cm3(Predicted)
• Storage Temp.: Sealed in dry,Room Temperature
• CAS DataBase Reference: diMethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-(CAS DataBase Reference)
• NIST Chemistry Reference: diMethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-(1246616-66-9)
• EPA Substance Registry System: diMethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-(1246616-66-9)

Safety Data

• Hazardous Substances Data: 1246616-66-9(Hazardous Substances Data)

Usage

Description

Dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate is a chemical compound that serves as a crucial intermediate in the synthesis of dolutegravir and its salts, which are utilized in antiretroviral medications.

Uses

Used in Pharmaceutical Industry:
Dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate is used as a key intermediate for the preparation of dolutegravir and dolutegravir salts, which are integral components in the development of antiretroviral medications. These medications are essential in the treatment of HIV/AIDS, helping to control the viral load and improve the quality of life for affected individuals.

Synthetic route

Dimethyl oxalate (553-90-2) + methyl 4-benzyloxy-2-((dimethylamino)methylene)acetoacetate (1246616-65-8) → dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9)

Conditions	Yield
With sodium t-butanolate In toluene at 105℃; for 6h;	90%
Stage #1: Dimethyl oxalate; methyl 4-benzyloxy-2-((dimethylamino)methylene)acetoacetate With sodium t-butanolate In 1,3-dimethyl-2-imidazolidinone at 20 - 30℃; for 7h; Inert atmosphere; Stage #2: With hydrogenchloride In 1,3-dimethyl-2-imidazolidinone; water at 20℃; for 15h;	85%
Stage #1: Dimethyl oxalate; methyl 4-benzyloxy-2-((dimethylamino)methylene)acetoacetate With sodium t-butanolate at 25 - 30℃; for 7h; Inert atmosphere; Stage #2: With hydrogenchloride at 20℃; for 15h;	85%
Stage #1: Dimethyl oxalate With 1,3-dimethyl-2-imidazolidinone; sodium methylate In methanol at 20℃; for 0.5h; Cooling with ice; Stage #2: methyl 4-benzyloxy-2-((dimethylamino)methylene)acetoacetate With sodium methylate In methanol at 20℃; for 4h;
With sodium t-butanolate In tetrahydrofuran at 0 - 30℃; for 2.16667h; Reagent/catalyst; Inert atmosphere; Cooling with ice;

Methyl 4-chloroacetoacetate (32807-28-6) → dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium tert-pentoxide / tetrahydrofuran / 2 h / 20 - 40 °C / Inert atmosphere 1.2: 2 h / 0 - 20 °C / Cooling with ice 2.1: 1,4-dioxane / 6 h / 20 °C 3.1: sodium t-butanolate / 1,3-dimethyl-2-imidazolidinone / 7 h / 20 - 30 °C / Inert atmosphere 3.2: 15 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium tert-pentoxide / tetrahydrofuran / 2 h / 40 °C / Inert atmosphere 1.2: 2 h / 0 - 20 °C 2.1: 1,4-dioxane / 6 h / 20 °C 3.1: sodium t-butanolate / 7 h / 25 - 30 °C / Inert atmosphere 3.2: 15 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: caesium carbonate / toluene / 12 h / 110 °C 2: sodium methylate / toluene / 5 h / 100 °C 3: sodium t-butanolate / toluene / 6 h / 105 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium tert-pentoxide / tetrahydrofuran / 2 h / 15 - 40 °C 1.2: 3 h / 40 °C / Cooling with ice 2.1: 1,3-dimethyl-2-imidazolidinone / 4 h / Cooling with ice 2.2: 1.5 h / 20 °C 3.1: sodium methylate; 1,3-dimethyl-2-imidazolidinone / methanol / 0.5 h / 20 °C / Cooling with ice 3.2: 4 h / 20 °C View Scheme
Multi-step reaction with 3 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 View Scheme

benzyl alcohol (100-51-6) → dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium tert-pentoxide / tetrahydrofuran / 2 h / 20 - 40 °C / Inert atmosphere 1.2: 2 h / 0 - 20 °C / Cooling with ice 2.1: 1,4-dioxane / 6 h / 20 °C 3.1: sodium t-butanolate / 1,3-dimethyl-2-imidazolidinone / 7 h / 20 - 30 °C / Inert atmosphere 3.2: 15 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium tert-pentoxide / tetrahydrofuran / 2 h / 40 °C / Inert atmosphere 1.2: 2 h / 0 - 20 °C 2.1: 1,4-dioxane / 6 h / 20 °C 3.1: sodium t-butanolate / 7 h / 25 - 30 °C / Inert atmosphere 3.2: 15 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: caesium carbonate / toluene / 12 h / 110 °C 2: sodium methylate / toluene / 5 h / 100 °C 3: sodium t-butanolate / toluene / 6 h / 105 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium tert-pentoxide / tetrahydrofuran / 2 h / 15 - 40 °C 1.2: 3 h / 40 °C / Cooling with ice 2.1: 1,3-dimethyl-2-imidazolidinone / 4 h / Cooling with ice 2.2: 1.5 h / 20 °C 3.1: sodium methylate; 1,3-dimethyl-2-imidazolidinone / methanol / 0.5 h / 20 °C / Cooling with ice 3.2: 4 h / 20 °C View Scheme
Multi-step reaction with 3 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 View Scheme

4-benzyloxy-3-oxobutyric acid methyl ester (82961-76-0) → dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 1,4-dioxane / 6 h / 20 °C 2.1: sodium t-butanolate / 1,3-dimethyl-2-imidazolidinone / 7 h / 20 - 30 °C / Inert atmosphere 2.2: 15 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: 1,4-dioxane / 6 h / 20 °C 2.1: sodium t-butanolate / 7 h / 25 - 30 °C / Inert atmosphere 2.2: 15 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: sodium methylate / toluene / 5 h / 100 °C 2: sodium t-butanolate / toluene / 6 h / 105 °C View Scheme
Multi-step reaction with 2 steps 1.1: 1,3-dimethyl-2-imidazolidinone / 4 h / Cooling with ice 1.2: 1.5 h / 20 °C 2.1: sodium methylate; 1,3-dimethyl-2-imidazolidinone / methanol / 0.5 h / 20 °C / Cooling with ice 2.2: 4 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: 1 h / 50 - 60 °C 2: sodium t-butanolate / tetrahydrofuran / 2.17 h / 0 - 30 °C / Inert atmosphere; Cooling with ice View Scheme

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) + 2,2-dimethoxyethylamine (22483-09-6) → 2,5-dimethyl 3-(benzyloxy)-1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridine-2,5-dicarboxylate (1357289-08-7)

Conditions	Yield
In toluene at 100℃; for 3h;	91%
In methanol for 6h; Reflux;	88%
With N-ethyl-N,N-diisopropylamine In methanol at 25℃; Reagent/catalyst; Solvent; Temperature;	85%
In methanol for 6h; Reflux;

tert-butyl (S)-(2-amino-3,3-diphenylpropyl)carbamate (1160984-36-0) + dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → dimethyl (S)-3-(benzyloxy)-1-(3-((tert-butoxycarbonyl)amino)-1,1-diphenylpropan-2-yl)-4-oxo-1,4-dihydropyridine-2,5-dicarboxylate (1246617-04-8)

Conditions	Yield
In toluene at 110℃; for 5h;	79%
In toluene at 110℃; for 5h;

t-butoxycarbonylhydrazine (870-46-2) + dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C21H24N2O8 (1246616-89-6)

Conditions	Yield
With acetic acid In toluene at 65℃; for 5h;	72.9%

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C15H12O7

Conditions	Yield
With water; lithium hydroxide In methanol Reagent/catalyst;	69.3%

tert-butyl (2S)-2-(aminomethyl)piperidine-1-carboxylate (475105-35-2) + dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C27H34N2O8

Conditions	Yield
In toluene at 100℃; for 5h;	65%

tert-butyl (2-amino-3-phenylpropyl)carbamate (943323-35-1) + dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C30H34N2O8 (1246617-09-3)

Conditions	Yield
In toluene at 100℃; for 2.5h;

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) + C20H26N2O2 (1246617-15-1) → C36H38N2O8 (1246617-16-2)

Conditions	Yield
In toluene at 110℃; for 1h;
In toluene at 110℃; for 1h;	667 mg

C16H24N2O3 (1246617-22-0) + dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C32H36N2O9 (1246617-23-1)

Conditions	Yield
In toluene at 100℃; for 4h;

C17H26N2O3 (825626-98-0) + dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C34H40N2O9 (1246617-79-7)

Conditions	Yield
In toluene at 100℃; for 1.5h;

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) + C23H30N2O3 (1246617-88-8) → C39H42N2O9 (1246617-89-9)

Conditions	Yield
In toluene at 100℃; for 2h;
In toluene at 100℃; for 2h;	391 mg

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C24H22N2O5 (1246617-10-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene / 2.5 h / 100 °C 2: hydrogenchloride / ethyl acetate / 0.5 h / 20 °C View Scheme

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C26H26N2O5 (1246617-11-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: toluene / 2.5 h / 100 °C 2.1: hydrogenchloride / ethyl acetate / 0.5 h / 20 °C 3.1: caesium carbonate / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 3.5 h / 20 °C View Scheme

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C25H24N2O5 (1246617-12-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: toluene / 2.5 h / 100 °C 2.1: hydrogenchloride / ethyl acetate / 0.5 h / 20 °C 3.1: caesium carbonate / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 3.5 h / 20 °C 4.1: sodium hydroxide / tetrahydrofuran; methanol / 1 h / 20 °C View Scheme

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C18H18N2O5 (1246617-13-9)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: toluene / 2.5 h / 100 °C 2.1: hydrogenchloride / ethyl acetate / 0.5 h / 20 °C 3.1: caesium carbonate / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 3.5 h / 20 °C 4.1: sodium hydroxide / tetrahydrofuran; methanol / 1 h / 20 °C 5.1: trifluoroacetic acid / 1 h / 20 °C 5.2: pH 3 View Scheme

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C30H26N2O5 (1246617-17-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene / 1 h / 110 °C 2: hydrogenchloride / ethyl acetate / 1 h / 20 °C View Scheme

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C31H28N2O5 (1246617-18-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: toluene / 1 h / 110 °C 2.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 3.1: caesium carbonate / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 1 h / 20 °C View Scheme

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C30H26N2O5 (1246617-19-5)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: toluene / 1 h / 110 °C 2.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 3.1: caesium carbonate / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 1 h / 20 °C 4.1: sodium hydroxide; water / tetrahydrofuran; methanol / 1 h / 20 °C View Scheme

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C23H20N2O5 (1246617-20-8)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: toluene / 1 h / 110 °C 2.1: hydrogenchloride / ethyl acetate / 1 h / 20 °C 3.1: caesium carbonate / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 1 h / 20 °C 4.1: sodium hydroxide; water / tetrahydrofuran; methanol / 1 h / 20 °C 5.1: trifluoroacetic acid / tetrahydrofuran / 1 h / 20 °C View Scheme

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C19H18N2O6 (1370239-00-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: toluene / 2 h / 100 °C 2.1: sodium hydroxide; water / ethanol; tetrahydrofuran / 1 h / 20 °C 3.1: trifluoroacetic acid / 1 h / 20 °C 3.2: pH 6 View Scheme

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C26H24N2O6 (1246617-82-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene / 2 h / 100 °C 2: sodium hydroxide; water / ethanol; tetrahydrofuran / 1 h / 20 °C View Scheme

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C20H22N2O8 (1246616-90-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: acetic acid / toluene / 5 h / 65 °C 2.1: water; lithium hydroxide / tetrahydrofuran; methanol / 2 h / 20 °C 2.2: Cooling in ice View Scheme

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → methyl (S)-4-benzhydryl-9-(benzyloxy)-1,8-dioxo-1,3,4,8-tetrahydro-2H-pyrido[1,2-a]pyrazine-7-carboxylate (1246617-05-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene / 5 h / 110 °C 2: hydrogenchloride / ethyl acetate / 1.5 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: toluene / 5 h / 110 °C 2: hydrogenchloride / ethyl acetate / 1.5 h / 20 °C View Scheme

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C31H28N2O5 (1246617-06-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: toluene / 5 h / 110 °C 2.1: hydrogenchloride / ethyl acetate / 1.5 h / 20 °C 3.1: caesium carbonate / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 3.5 h / 20 °C View Scheme

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C30H26N2O5 (1246617-07-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: toluene / 5 h / 110 °C 2.1: hydrogenchloride / ethyl acetate / 1.5 h / 20 °C 3.1: caesium carbonate / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 3.5 h / 20 °C 4.1: sodium hydroxide / tetrahydrofuran; methanol / 1.5 h / 20 °C 4.2: 3.5 h / 20 °C View Scheme

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → C23H20N2O5 (1246617-08-2)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: toluene / 5 h / 110 °C 2.1: hydrogenchloride / ethyl acetate / 1.5 h / 20 °C 3.1: caesium carbonate / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 3.5 h / 20 °C 4.1: sodium hydroxide / tetrahydrofuran; methanol / 1.5 h / 20 °C 4.2: 3.5 h / 20 °C 5.1: trifluoroacetic acid / 1 h / 20 °C 5.2: pH 3 View Scheme

dimethyl 3-(benzyloxy)-4-oxo-4H-pyran-2,5-dicarboxylate (1246616-66-9) → (4R,12aS)-7-(benzyloxy)-N-(2,4-difluorobenzyl)-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1′,2’:4,5]-pyrazino[2,1-b][1,3]oxazine-9-carboxamide (1206102-11-5)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: methanol / 6 h / Reflux 2.1: formic acid; sulfuric acid / water / 3 h / 20 °C 2.2: 5 °C 3.1: acetic acid / methanol; toluene / 3 h / 90 °C 4.1: acetic acid / toluene / 7 h / 100 °C View Scheme
Multi-step reaction with 4 steps 1.1: methanol / 6 h / Reflux 2.1: acetic acid / toluene / 7 h / 90 °C 3.1: formic acid; sulfuric acid / toluene; water / 3 h / 20 °C 3.2: 5 °C 4.1: acetic acid / methanol; toluene / 2 h / 90 °C View Scheme
Multi-step reaction with 5 steps 1: N-ethyl-N,N-diisopropylamine / methanol / 25 °C 2: acetic acid / toluene / 90 - 95 °C 3: acetic acid; methanesulfonic acid / acetonitrile / 60 - 65 °C / Inert atmosphere 4: acetonitrile / 2 h / 25 °C / Inert atmosphere 5: acetonitrile / 60 - 65 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: methanol / 6 h / Reflux 2.1: sulfuric acid / water; formic acid / 2.5 h / 5 °C 2.2: 2.5 h / 100 °C 2.3: 1.5 h / 5 °C 3.1: acetic acid / toluene / 5 h / 100 °C View Scheme

Upstream product

• 553-90-2 Dimethyl oxalate 
• 1246616-65-8 methyl 4-benzyloxy-2-((dimethylamino)methylene)acetoacetate 
• 82961-76-0 4-benzyloxy-3-oxobutyric acid methyl ester 
• 100-51-6 benzyl alcohol 
• 32807-28-6 Methyl 4-chloroacetoacetate 

Downstream Products

• 1246616-89-6 C₂₁H₂₄N₂O₈ 
• 1246617-09-3 C₃₀H₃₄N₂O₈ 
• 1246617-04-8 dimethyl (S)-3-(benzyloxy)-1-(3-((tert-butoxycarbonyl)amino)-1,1-diphenylpropan-2-yl)-4-oxo-1,4-dihydropyridine-2,5-dicarboxylate 
• 1246617-16-2 C₃₆H₃₈N₂O₈ 
• 1246617-23-1 C₃₂H₃₆N₂O₉ 
• 1246617-79-7 C₃₄H₄₀N₂O₉ 
• 1246617-89-9 C₃₉H₄₂N₂O₉ 
• 1246617-10-6 C₂₄H₂₂N₂O₅ 
• 1246617-11-7 C₂₆H₂₆N₂O₅ 
• 1246617-12-8 C₂₅H₂₄N₂O₅ 
• 1246617-13-9 C₁₈H₁₈N₂O₅ 
• 1246617-17-3 C₃₀H₂₆N₂O₅ 
• 1246617-18-4 C₃₁H₂₈N₂O₅ 
• 1246617-19-5 C₃₀H₂₆N₂O₅ 

Relevant articles and documents

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.

Synthesis method of dolutegravir intermediate, and related substance detection method thereof

The invention discloses a synthesis method of a dolutegravir intermediate, and a related substance detection method thereof. 4-chloroacetoacetic acid methyl ester and phenylcarbinol are adopted as starting materials, and the dolutegravir intermediate i is obtained through four steps of reaction; the reaction conditions are simple, only methylbenzene is used as a solvent in reaction, the raw materials are easy to get, the obtained product is treated and purified through column chromatography, the yield of the product obtained by each step reaches up to 90 percent or above, and the synthesis method is suitable for industrial production; the related substance detection method of the dolutegravir intermediate i adopts high performance liquid chromatography; through testing, the content of thedolutegravir intermediate i related substance is 99.6 percent, the separation degree of each impurity is larger than 3.0, and the separation degree is better.

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