80841-78-7

Basic information

• Product Name: 4-Cloromethyl-5-methyl-1,3-dioxol-2-one
• Synonyms: DMDO-CL;4-Cloromethyl-5-methyl-1,3-dioxol-2-one;4-CHLOROMETHYL-5-METHYL-2-OXO-1,3-DIOXOLE;4-CHLOROMETHYL-5-METHYL-1,3-DIOXOL-2-ONE;4-CHLOROMETHYL-5-METHYL-1,3-DIOXOLEN-2-ONE;DMDO CL (4-METHYL-5-CHLOROMETHYL-1,3-DIOXOL-2-ONE);4-Chloromethyl-5-Methyl-1,3-Dioxol-2-One(Dmdo-Cl);4-Chloromethyl-5-Methyl-1,3-Dioxocyclopenten-2-one
• CAS NO: 80841-78-7
• Molecular Formula: C₅H₅ClO₃
• Molecular Weight: 148.54
• EINECS: 1592732-453-0
• Product Categories: Chemical intermediate for Olmesartane;INTERMEDIATESOF;Carbonates;Carbonyl Compounds;Organic Building Blocks;Pharmaceutical Intermediates
• Mol File: 80841-78-7.mol

Chemical Properties

• Boiling Point: >90℃/2mm
• Flash Point: 129 °C
• Appearance: /
• Density: 1.362 g/cm³
• Vapor Pressure: 2.085mmHg at 25°C
• Refractive Index: 1.4760-1.4820
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• BRN: 4798926
• CAS DataBase Reference: 4-Cloromethyl-5-methyl-1,3-dioxol-2-one(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Cloromethyl-5-methyl-1,3-dioxol-2-one(80841-78-7)
• EPA Substance Registry System: 4-Cloromethyl-5-methyl-1,3-dioxol-2-one(80841-78-7)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38
• Safety Statements: 26
• WGK Germany: 3
• Hazardous Substances Data: 80841-78-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
4-Chloromethyl-5-methyl-1,3-dioxol-2-one is used as a key reagent in the preparation of angiotensin II receptor antagonists, such as Olmesartan Medoxomil (O550000), for the treatment of hypertension and heart failure. It plays a vital role in the development of these medications due to its unique chemical properties that facilitate the synthesis process.
Additionally, 4-Chloromethyl-5-methyl-1,3-dioxol-2-one is utilized in the preparation of prodrugs of ampicillin, a widely used antibiotic, enhancing its effectiveness and bioavailability in treating bacterial infections. Its application in prodrug development highlights its versatility and importance in the pharmaceutical field.

InChI:InChI=1/C5H5ClO3/c1-3-4(2-6)9-5(7)8-3/h2H2,1H3

Synthetic route

4,5-Dimethyl-1,3-dioxole-2-one (37830-90-3) → 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7)

Conditions	Yield
With chlorine In 1,2-dichloro-ethane for 0.5h; Solvent; Reagent/catalyst; Reflux; Molecular sieve;	89.3%
With N-chloro-succinimide In tetrachloromethane for 80h; Ambient temperature; Irradiation;	9.2%
With chlorine; copper 1.) dichloromethane, 90 min, reflux, 2.) dichloromethane, 2 h, reflux; Yield given. Multistep reaction;
With sulfuryl dichloride In dichloromethane
With N-chloro-succinimide; dibenzoyl peroxide at 90℃; for 5.5h; Temperature; Solvent; Large scale;	326 g

4-chloro-4-methyl-5-methylene-1,3-dioxolane-2-one (95579-71-8) → 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7)

Conditions	Yield
at 75 - 80℃; for 4h;	87%

4,5-Dimethyl-1,3-dioxole-2-one (37830-90-3) → 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) + 4-chloro-4-methyl-5-methylene-1,3-dioxolane-2-one (95579-71-8) + 4,5-dimethyl-4,5-dichloro-1,3-dioxolan-2-one (129482-56-0)

Conditions	Yield
With chlorine In dichloromethane at 43 - 45℃; Product distribution; further solvents;	A 1.4 % Chromat. B 87.5 % Chromat. C n/a

methyl (7S)-6-N-((2′S,4′R)-4′-(cyclopropylmethyl)piperidine-2′-carbonyl)-7-deoxy-7-(4-(pyrimidin-5-yl)phenylthio)-α-thiolincosaminide (1088409-50-0) + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → methyl 6-N-((2S,4R)-4-cyclopropylmethyl-1-((5-methyl-2-oxo-1,3-dioxol-4-yl)methyl)pipecoloyl)-7-deoxy-7-epi-7-(4-(pyrimidin-5-yl)phenylthio)-1-thio-α-lincosamide (1088410-47-2)

Conditions	Yield
With sodium carbonate In N,N-dimethyl-formamide at 20℃; for 1.5h;	100%

Furopenem (122547-49-3) + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → faropenem medoxomil

Conditions	Yield
With sodium hydrogencarbonate; potassium iodide; benzyltri(n-butyl)ammonium chloride In tetrahydrofuran at 30 - 55℃; for 5h;	99.11%
With sodium hydrogencarbonate; potassium iodide; tetrabutyl-ammonium chloride In acetone at 50℃; for 4h; Conversion of starting material;	94.2%
With benzyltri(n-butyl)ammonium chloride; sodium hydrogencarbonate; potassium iodide In tetrahydrofuran at 30 - 55℃; for 6h; Product distribution / selectivity;	70%
With sodium hydrogencarbonate; benzyltri(n-butyl)ammonium chloride In tetrahydrofuran at 50℃; for 4h; Conversion of starting material;	36.7%

(3S,4S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-3-((2,5,8,11-tetraoxatetradecan-14-oyl)oxy)-11-((benzyloxy)carbonyl)-4,6a,6b,8a,11,14b-hexamethyl-14-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-icosahydropicene-4-carboxylic acid + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → 2-benzyl 9-((5-methyl-2-oxo-1,3-dioxol-4-yl)methyl) (2S,4aS,6aS,6bR,8aR,9S,10S,12aS,12bR,14bR)-10-((2,5,8,11-tetraoxatetradecan-14-oyl)oxy)-2,4a,6a,6b,9,12a-hexamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2,9-dicarboxylate

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 60℃; for 48h;	99%

(E)-(2S,3S)-3-[(S)-2-(4-but-2-ynyloxyphenyl)-1-methoxycarbonylethylcarbamoyl]-2-hydroxy-2-(2-hydroxyethyl)-12-oxononadec-4-enoic acid potassium salt + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → C41H57NO12

Conditions	Yield
With sodium iodide In N,N-dimethyl-formamide at 40℃; for 1h; Inert atmosphere;	97%

(3S,4aS,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-((benzyloxy)carbonyl)- 4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9, 10,11,12,12a,14,14a,14b-icosahydropicene-3-carboxylic acid + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → 2-benzyl 10-((5-methyl-2-oxo-1,3-dioxol-4-yl)methyl) (2S,4aS,6aS,6bR,8aS,10S,12aS,12bR,14bR)-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2,10-dicarboxylate

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 60℃; for 2h;	97%

ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1-({2'-[1-(triphenylmethyl)-1H-1,2,3,4-tetrazol-5-yl]-[1,1'-biphenyl]-4-yl}methyl)-1H-imidazole-5-carboxylate (144690-33-5) + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → trityl olmesartan medoxomil (144690-92-6)

Conditions	Yield
Stage #1: ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1-({2'-[1-(triphenylmethyl)-1H-1,2,3,4-tetrazol-5-yl]-[1,1'-biphenyl]-4-yl}methyl)-1H-imidazole-5-carboxylate With lithium hydroxide monohydrate In tetrahydrofuran at 20℃; for 18h; Large scale; Stage #2: 4-chloromethyl-5-methyl-1,3-dioxol-2-one With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 20 - 40℃; for 2h; Large scale;	96.5%
Stage #1: ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1-({2'-[1-(triphenylmethyl)-1H-1,2,3,4-tetrazol-5-yl]-[1,1'-biphenyl]-4-yl}methyl)-1H-imidazole-5-carboxylate With sodium hydroxide In ethanol at 20 - 25℃; Stage #2: 4-chloromethyl-5-methyl-1,3-dioxol-2-one With potassium carbonate In N,N-dimethyl acetamide at 45 - 50℃; for 4h;	88%
Stage #1: ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1-({2'-[1-(triphenylmethyl)-1H-1,2,3,4-tetrazol-5-yl]-[1,1'-biphenyl]-4-yl}methyl)-1H-imidazole-5-carboxylate With sodium hydroxide In acetone at 50 - 60℃; for 5h; Green chemistry; Stage #2: 4-chloromethyl-5-methyl-1,3-dioxol-2-one With potassium iodide In acetone at 20 - 60℃; for 1h; Green chemistry;	85.8%

4-(1-hydroxy-1-methylethyl)-2-propyl-1-(4-(2-(1-(triphenylmethyl)tetrazol-5-yl)phenyl)phenyl)methylimidazole-5-carboxylic acid (761404-85-7) + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → trityl olmesartan medoxomil (144690-92-6)

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl acetamide at 0 - 45℃; for 3h; Inert atmosphere;	94%
Stage #1: 4-(1-hydroxy-1-methylethyl)-2-propyl-1-(4-(2-(1-(triphenylmethyl)tetrazol-5-yl)phenyl)phenyl)methylimidazole-5-carboxylic acid With potassium carbonate In N,N-dimethyl-formamide at 20℃; Autoclave; Stage #2: 4-chloromethyl-5-methyl-1,3-dioxol-2-one With potassium iodide In N,N-dimethyl-formamide at 20℃;	91.6%
With potassium carbonate; potassium iodide In acetone Product distribution / selectivity; Reflux;
In water; acetone at 48 - 52℃; for 5h; Product distribution / selectivity;
With potassium bromide In N,N-dimethyl acetamide at 15 - 50℃; for 8.6h; Time; Green chemistry;	23.2 g

sodium 4-(2-hydroxypropan-2-yl)-2-propyl-1-({2'-[1-(triphenylmethyl)-1H-1,2,3,4-tetrazol-5-yl]-[1,1'-biphenyl]-4-yl}methyl)-1H-imidazole-5-carboxylate (879097-59-3) + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → trityl olmesartan medoxomil (144690-92-6)

Conditions	Yield
With potassium carbonate In N,N-dimethyl acetamide at 5 - 10℃; for 4h;	93%
With sodium carbonate In N,N-dimethyl acetamide at 45 - 50℃; Large scale reaction;	80%
With potassium carbonate In N,N-dimethyl-formamide at 0 - 85℃; for 4h;
With sodium iodide In N,N-dimethyl-formamide at 55℃; for 7.5h;	45g
With iodine; sodium carbonate at 50℃; under 75.0075 Torr; Inert atmosphere; Large scale;	53.6 kg

fenofibric acid (42017-89-0) + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl-2‑(4‑(4-chlorobenzoyl)phenoxy)-2-methylpropanoate (1319719-25-9)

Conditions	Yield
With potassium carbonate In N,N-dimethyl acetamide at 65℃;	93%
With sodium carbonate In N,N-dimethyl acetamide at 30℃; for 17h; Inert atmosphere;	83%

2-(((3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-((benzhydryloxy)carbonyl)-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-icosahydropicen-3-yl)oxy)acetic acid + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → benzhydryl (2S,4aS,6aS,6bR,8aR,10S,12aS,12bR,14bR)-2,4a,6a,6b,9,9,12a-heptamethyl-10-(2-((5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy)-2-oxoethoxy)-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxylate

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 60℃;	93%

N-hydroxyphthalimide (524-38-9) + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → 2-[(5-methyl-2-oxo-2H-1,3-dioxol-4-yl)methoxy]-2,3-dihydro-1H-isoindole-1,3-dione

Conditions	Yield
Stage #1: N-hydroxyphthalimide With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: 4-chloromethyl-5-methyl-1,3-dioxol-2-one In N,N-dimethyl-formamide at 0 - 70℃; Inert atmosphere;	92%
Stage #1: N-hydroxyphthalimide With sodium hydride In N,N-dimethyl-formamide at 0℃; Inert atmosphere; Stage #2: 4-chloromethyl-5-methyl-1,3-dioxol-2-one In N,N-dimethyl-formamide at 70℃; for 1h; Inert atmosphere;	92%

potassium 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl]biphenyl-4-yl]methyl]imidazole-5-carboxylate (936114-12-4) + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → trityl olmesartan medoxomil (144690-92-6)

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl acetamide at 0 - 45℃; for 3h;	91%
With potassium iodide In butanone at 50℃; for 7.5h;	86%
With potassium iodide In butanone at 50℃; for 20h;	84.4%
Stage #1: potassium 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl]biphenyl-4-yl]methyl]imidazole-5-carboxylate With sodium carbonate; potassium iodide In acetone at 25 - 30℃; for 0.166667h; Stage #2: 4-chloromethyl-5-methyl-1,3-dioxol-2-one In acetone at 45 - 50℃; for 12h;	76 g
With iodine; potassium carbonate at 50℃; under 75.0075 Torr; Inert atmosphere; Large scale;	54.06 kg

4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) + atovaquone (95233-18-4) → 3-(5-methyl-2-oxo-1,3-dioxol-4-yl)methyloxy-2-trans-[(4-chlorophenyl)cyclohexyl][1,4]naphthoquinone (1445850-06-5)

Conditions	Yield
With potassium carbonate In acetonitrile at 60 - 65℃; Concentration;	90%

4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) + trans-atovaquone → 3-(5-methyl-2-oxo-1,3-dioxol-4-yl)methyloxy-2-trans-[(4-chlorophenyl)cyclohexyl][1,4]naphthaquinone

Conditions	Yield
With potassium carbonate In acetonitrile at 60 - 65℃; Concentration;	90%

4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) + ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[2'-(2-triphenylmethyl-2H-tetrazol-5-yl)biphenyl-4-yl]methyl-1H-imidazole-5-carboxylate (172875-59-1) → olmesartan medoxomil (144689-63-4)

Conditions	Yield
Stage #1: ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[2'-(2-triphenylmethyl-2H-tetrazol-5-yl)biphenyl-4-yl]methyl-1H-imidazole-5-carboxylate With sodium hydroxide In N,N-dimethyl acetamide at 10 - 15℃; for 8h; Stage #2: 4-chloromethyl-5-methyl-1,3-dioxol-2-one With potassium carbonate In N,N-dimethyl acetamide at 0 - 65℃; for 10h;	90%

4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) + 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2'-[2-(triphenylmethyl)-2H-tetrazol-5yl]biphenyl-4-yl]methyl]imidazole-5-carboxylic acid lithium salt → (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl4-(1-hydroxy-1-methylethyl)-2-propyl-1-[2′-(2-triphenylmethyl-2H-tetrazol-5-yl)biphenyl-4-yl]methyl-1H-imidazole-5-carboxylate (1020157-01-0)

Conditions	Yield
With potassium carbonate In N,N-dimethyl acetamide at 20 - 50℃; for 4h;	88%
Stage #1: 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2'-[2-(triphenylmethyl)-2H-tetrazol-5yl]biphenyl-4-yl]methyl]imidazole-5-carboxylic acid lithium salt With triethylamine In ISOPROPYLAMIDE at 20℃; for 0.5h; Stage #2: 4-chloromethyl-5-methyl-1,3-dioxol-2-one In ISOPROPYLAMIDE at 10 - 55℃; for 4h;	75%

trityl chloride (76-83-5) + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) + methyl 2-ethoxy-1-((2′-(N′-hydroxycarbamimidoyl)-biphenyl-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate (147403-65-4) → (5-methyl-2-oxo-2H-1,3-dioxol-4yl)methyl 2-ethoxy-1-[(4-(2-[N-hydroxy-carbamimidoyl]phenyl)phenyl)-methyl]-1H-1,3-benzodiazole-7-carboxylate (1449029-77-9)

Conditions

Yield

Stage #1: trityl chloride; methyl 2-ethoxy-1-((2′-(N′-hydroxycarbamimidoyl)-biphenyl-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate With triethylamine In dichloromethane at 25 - 30℃; for 16h; Large scale; Stage #2: With sodium hydroxide In tetrahydrofuran; methanol; water at 25 - 45℃; for 8h; Large scale; Stage #3: 4-chloromethyl-5-methyl-1,3-dioxol-2-one Reagent/catalyst; Temperature; Large scale; Further stages;

88%

4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl iodide (80841-79-8)

Conditions	Yield
With sodium iodide In acetonitrile at 30℃; for 0.5h;	87%
With sodium iodide In butanone at 20 - 60℃; for 1.5h;	77%

(3S,4S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-[(benzhydryloxyoxy)carbonyl]-3-(4,4-difluoropiperidin-1-yl)-4,6a,6b,8a,11,14b-hexamethyl-14-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-icosahydropicene-4-carboxylic acid + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → 2-benzhydryl 9-(5-methyl-2-oxo-2H-1,3-dioxol-4-yl)methyl (2S,4aS,6aS,6bR,8aR,9S,10S,12aS,12bR,14bR)-10-(4,4-difluoropiperidin-1-yl)-2,4a,6a,6b,9,12a-hexamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2,9-dicarboxylate

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 60℃; for 1h;	87%

(4S)-3-oxo-8-[2-(8-tert-butoxycarbonyl-5,6,7,8-tetrahydroimidazo[1,2-a]-pyrimidin-2-yl)ethoxy]-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-4-acetic acid (1152636-93-5) + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → (5-methyl-2-oxo-[1,3]dioxolen-4-yl)methyl (4S)-3-oxo-8-[2-(8-tert-butoxycarbonyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidin-2-yl)ethoxy]-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-4-acetate (1152636-96-8)

Conditions	Yield
Stage #1: (4S)-3-oxo-8-[2-(8-tert-butoxycarbonyl-5,6,7,8-tetrahydroimidazo[1,2-a]-pyrimidin-2-yl)ethoxy]-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-4-acetic acid; 4-chloromethyl-5-methyl-1,3-dioxol-2-one With sodium hydrogencarbonate In N,N-dimethyl-formamide for 2.5h; Cooling with ice; Inert atmosphere; Stage #2: With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 6h; Stage #3: 4-chloromethyl-5-methyl-1,3-dioxol-2-one In N,N-dimethyl-formamide at 20℃; for 15.5h;	86%
Stage #1: (4S)-3-oxo-8-[2-(8-tert-butoxycarbonyl-5,6,7,8-tetrahydroimidazo[1,2-a]-pyrimidin-2-yl)ethoxy]-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-4-acetic acid With sodium hydrogencarbonate In water; N,N-dimethyl-formamide for 2.5h; Inert atmosphere; Cooling with ice; Stage #2: 4-chloromethyl-5-methyl-1,3-dioxol-2-one With potassium carbonate at 20℃; for 21.5h;	86%

2-(((3S,4R,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-((benzhydryloxy)carbonyl)-3-hydroxy-4,6a,6b,8a,11,14b-hexamethyl-14-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-icosahydropicen-4-yl)methoxy)acetic acid + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → benzhydryl (2S,4aS,6aS,6bR,8aR,9R,10S,12aS,12bR,14bR)-10-hydroxy-2,4a,6a,6b,9,12a-hexamethyl-9-((2-((5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy)-2-oxoethoxy)methyl)-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxylate

Conditions	Yield
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 50℃; for 1h;	86%

4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) + azilsartan (147403-03-0) → C35H28N4O11

Conditions	Yield
With sodium carbonate; sodium iodide In N,N-dimethyl acetamide at 35℃; for 3h; Reagent/catalyst; Solvent;	85.9%

5-(((tert-butoxycarbonyl)amino)methyl)-6-isobutyl-2-methyl-4-(4-methylphenyl)nicotinic acid (851577-43-0) + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 5-{[(tert-butoxycarbonyl)amino]methyl}-6-isobutyl-2-methyl-4-(4-methylphenyl)nicotinate (851581-35-6)

Conditions	Yield
With potassium carbonate In DMF (N,N-dimethyl-formamide) at 20℃; for 1h;	85%

(6-{(pyridin-2-ylsulfonyl)[4-(thiazol-2-yl)benzyl]aminomethyl}pyridin-2-ylamino)-acetic acid (1187450-51-6) + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → [(5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl] (6-{(pyridin-2-ylsulfonyl)[4-(thiazol-2-yl)benzyl]aminomethyl}pyridin-2-ylamino)acetate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 15h;	84%

(E)-1-[[2′-[[N-(2-chlorotrityl)]-1H-tetrazol-5-yl]biphenyl-4-yl]methyl]imidazole-4-acrylic acid + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → (E)-(5-methyl-2-oxo-1,3-dioxol)methyl-1-[[2′-[[N-(2-chlorotrityl)]-1H-tetrazol-5-yl]biphenyl-4-yl]-methyl]imidazole-4-acrylate

Conditions	Yield
Stage #1: (E)-1-[[2′-[[N-(2-chlorotrityl)]-1H-tetrazol-5-yl]biphenyl-4-yl]methyl]imidazole-4-acrylic acid With potassium carbonate In N,N-dimethyl acetamide at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-chloromethyl-5-methyl-1,3-dioxol-2-one In N,N-dimethyl acetamide for 4h; Inert atmosphere;	84%

5-({(3R)-1-[(trans-4-{(1S)-1-[(tert-butoxycarbonyl)amino]-2-fluoroethyl}cyclohexyl)carbonyl]-3-phenyl-L-prolyl}amino)-1H-indole-2-carboxylic acid + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → (5-methyl-2-oxo-1,3-disoxol-4-yl)methyl 5-({(3R)-1-(trans-4-{(1S)-1-[(tert-butoxycarbonyl)amino]-2-fluoroethyl}cyclohexyl)carbonyl-3-phenyl-L-prolyl}amino)-1H-indole-2-carboxylate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	84%

benzhydryl (2S,4aS,6aS,6bR,8aR,9S,10S,12aS,12bR,14bR)-10-acetoxy-9-isocyanato-2,4a,6a,6b,9,12a-hexamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxylate + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → benzhydryl (2S,4aS,6aS,6bR,8aR,9S,10S,12aS,12bR,14bR)-10-acetoxy-2,4a,6a,6b,9,12a-hexamethyl-9-((((5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy)carbonyl)amino)-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxylate

Conditions	Yield
With chloro-trimethyl-silane In dichloromethane at 20℃; Further stages;	84%

4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) + p-Chlorothiophenol (106-54-7) → 4-(4-Chlorophenyl)thiomethyl-5-methyl-1,3-dioxol-2-one (111738-34-2)

Conditions	Yield
With triethylamine In dichloromethane	83%
With triethylamine In dichloromethane; ethyl acetate

Upstream product

• 95579-71-8 4-chloro-4-methyl-5-methylene-1,3-dioxolane-2-one 
• 37830-90-3 4,5-Dimethyl-1,3-dioxole-2-one 

Downstream Products

• 111738-26-2 2-Chloro-5-((5-methyl-2-oxo-1,3-dioxol-4-yl)methylthio)benzoic Acid 
• 111738-31-9 5-Methyl-4-(4-methylphenyl)thiomethyl-1,3-dioxol-2-one 
• 863031-21-4 Azilsartan medoxomil 
• 144690-92-6 trityl olmesartan medoxomil 
• 1227626-49-4 C₄₇H₄₀N₆O₆ 
• 1415335-13-5 C₂₄H₂₄ClNO₇ 
• 1394050-47-5 C₃₄H₄₃NO₉ 
• 91526-18-0 4-hydroxymethyl-5-methyl-[1,3]dioxol-2-one 
• 1383005-47-7 (2R,4R)-4-[(5-acetyl-2H-pyrazole-3-carbonyl)amino]-5-biphenyl-4-yl-2-hydroxypentanoic acid 5-methyl-2-oxo-[1,3]-dioxol-4-ylmethyl ester trifluoroacetate 
• 1378863-72-9 (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-(1-hydroxy-1-methylpropyl)-2-propyl-1-((2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-1H-imidazole-5-carboxylate 
• 1391052-99-5 (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 4-isopropenyl-2-propyl-1-[[2'-[2-(triphenylmethyl)-2H-tetrazol-5-yl]biphenyl-4-yl]methyl]imidazole-5-carboxylate 
• 1319719-25-9 (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl-2?(4?(4-chlorobenzoyl)phenoxy)-2-methylpropanoate 
• 1331782-60-5 1-((((1-(2-((5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy)-2-oxoethyl)cyclohexyl)methyl)carbamoyl)oxy)ethyl 2-(2-(nitrooxy)ethoxy)acetate 
• 1268602-81-8 (5-methyl-2-oxo-1,3-dioxolene-4-yl)methyl 1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolylacetate 

Relevant articles and documents

Preparation method of olmesartan medoxomil key intermediate

The invention discloses a preparation method of an olmesartan medoxomil key intermediate, and belongs to the technical field of medicine synthesis. The key points of the technical scheme are as follows: triphosgene with relatively low toxicity is adopted to replace gaseous phosgene, so that the problems of storage and transportation are solved; and a molecular distillation technology is utilized to treat the crude product, so that the occurrence of a polymer at high temperature is avoided, and a high-yield product is obtained.

Method for catalytically synthesizing high-purity 4-chloromethyl-5-methyl-1,3-dioxol-2-one

The invention belongs to the technical field of medicine synthesis, and particularly relates to a method for catalytically synthesizing high-purity 4-chloromethyl-5-methyl-1,3-dioxol-2-one. The methodcomprises the steps: taking 4,5-dimethyl-1,3-dioxol-2-one as a raw material, taking solid alkali as a catalyst, heating and refluxing in the presence of an organic solvent, taking a chlorine dichloroethane solution as a chlorination reagent, and performing reflux reaction after dropwise adding is finished; after the reaction is finished, washing with water, layering, extracting, drying an organicphase with anhydrous magnesium sulfate, filtering, performing reflux rearrangement on filtrate for 2-4 h, and after the reaction is monitored to be finished by TLC, carrying out reduced pressure distillation, separation and nitrogen purging on the reaction liquid to obtain a 4-chloromethyl-5-methyl-1,3-dioxol-2-one crude product; and purifying to obtain the 4-chloromethyl-5-methyl-1,3-dioxol-2-one. The method has the characteristics of low cost, short reaction period, easiness in operation, high product purity and high yield.

A 4 - chloro methyl -5 - methyl - 1, 3 - dioxo heterocyclic pentene -2 - one purification method

The invention discloses a purification method of 4-chloromethyl-5-methyl-1,3-dioxole-2-ketone. The purification method comprises the following steps of dissolving a crude product of 4-chloromethyl group-5-methyl-1,3-dioxole-2-ketone into a mixed solvent of methyl alcohol, ethyl alcohol, isopropyl alcohol and tertiary butanol for crystallizing for 0-24 hours at a temperature of -10-0 DEG C, and filtering to acquire the 4-chloromethyl-5-methyl-1,3-dioxole-2-ketone. The purification method has the characteristics of low cost, good refining effect, high yield, low requirement on equipment and simplicity and convenience in operation and is suitable for industrial production.

Preparation method for 4-chloromethyl-5-methyl-1,3-dioxol-2-one

The invention specifically relates to a preparation method for 4-chloromethyl-5-methyl-1,3-dioxol-2-one, belonging to the technical field of chemical synthesis. According to the invention, acetoin isused as a raw material and reacts with chloroformate in a solvent under the action of a catalyst so as to produce DMDO; the prepared DMDO is further reacts with a chlorinating reagent and a free radical initiator in a solvent to obtain a crude DMDO-Cl product; and then rectification is carried out so as to obtain a fine DMDO-Cl product. The fine DMDO-Cl product has a purity of 99% or above.

A Convenient and Practical Preparation of 4-Chloromethyl-5-methyl-1,3-dioxol-2-one

A new synthetic method for 4-chloromethyl-5-methyl-1,3-dioxol-2-one (1c), which is useful for preparing prodrugs, has been developed.Ene-chlorination of 4,5-dimethyl-1,3-dioxol-2-one (2) with chlorine or sulfuryl chloride afforded 4-chloro-4-methyl-5-methylene-1,3-dioxolan-2-one (3) in good yield.Compound 3 underwent allylic rearrangement to afford 1c quantitatively.The overall yield of 1c from 2 was approximately 80percent. Keywords---4-chloromethyl-5-methyl-1,3-dioxol-2-one; 4,5-dimethyl-1,3-dioxol-2-one; 4-chloro-4-methyl-5-methylene-1,3-dioxolan-2-one; ene-chlorination; allylic rearrangement; (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl group; promoiety; prodrug

4-Chloro-4-methyl-5-methylene-1,3-dioxolane-2-one

4-Chloro-4-methyl-5-methylene-1,3-dioxolane-2-one is useful as an intermediate for the synthesis of 4-chloromethyl-5-methyl-1,3-dioxolene-2-one which, in turn, finds use as a modifying agent for making various prodrugs. Said intermediate compound gives said objective compound in a good yield by a rearrangement reaction.

1,3-Dioxolen-2-one derivatives and process for production thereof

A 1,3-dioxolen-2-one derivative of the general formula STR1 wherein R1 represents a hydrogen atom, a methyl group, or an aryl group, R2 represents a hydrogen atom, or may be taken together with R1 to form a divalent carbon chain residue, and x represents a halogen atom. The above compounds can be prepared by reacting a compound of the general formula STR2 with a halogenating agent, and are useful as protective group-introducing reagents for introducing protective groups into reagents in various chemical reactions, or as modifiers for prodrug preparation in medicine.