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
• Article Data: 8

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

Chemical Properties

4-Cloromethyl-5-methyl-1,3-dioxol-2-one is Pale Yellow Oil

Uses

4-Chloromethyl-5-methyl-1,3-dioxol-2-one is an important reagent in the preparation of angiotensin II receptor antagonist such as Olmesratan Medoxomil (O550000). 4-Chloromethyl-5-methyl-1,3-dioxol-2-one is also used in the preparation of prodrugs of ampicillin.

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

• 111738-22-8 Sodium 4-((5-Methyl-2-oxo-1,3-dioxol-4-yl)methylthio)benzenesulfonate 
• 111738-32-0 5-Methyl-4-(4-nitrophenyl)thiomethyl-1,3-dioxol-2-one 
• 144689-63-4 olmesartan 
• 1020157-01-0 (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 
• 1415335-13-5 C₂₄H₂₄ClNO₇ 
• 1227626-49-4 C₄₇H₄₀N₆O₆ 
• 144690-46-0 (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl 1-[(2'-t-butoxycarbonylbiphenyl-4-yl)methyl]-4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate 
• 123447-62-1 prulifloxacin 
• 111738-34-2 4-(4-Chlorophenyl)thiomethyl-5-methyl-1,3-dioxol-2-one 
• 111738-31-9 5-Methyl-4-(4-methylphenyl)thiomethyl-1,3-dioxol-2-one 
• 111738-33-1 5-Methyl-4-phenylthiomethyl-1,3-dioxol-2-one 
• 111738-23-9 Sodium 3-((5-Methyl-2-oxo-1,3-dioxol-4-yl)methylthio)benzenesulfonate 
• 111738-26-2 2-Chloro-5-((5-methyl-2-oxo-1,3-dioxol-4-yl)methylthio)benzoic Acid 
• 111738-30-8 4-(4-Methoxyphenyl)thiomethyl-5-methyl-1,3-dioxol-2-one 

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.

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.

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