124750-51-2

Basic information

• Product Name: 5-(4'-Bromomethyl-1,1'-biphenyl-2-yl)-1-triphenylmethyl-1H-tetrazole
• Synonyms: N-(Triphenylmethyl)-5-(4'-bromomethylbiphenyl-2-yl-)terazole;N-(TRIPHENYLMETHYL)-5-(4'-BROMOMETHYLBIPHENYL-2-YL) TETRAZOLE;5-(4'-BROMOMETHYL-1,1'-BIPHENYL-2-YL)-1-TRIPHENYLMETHYL-1H-TETRAZOLE;5-(4'-BROMOMETHYL-BIPHENYL-2-YL)-1-TRITYL-1H-TETRAZOLE;1H-Tetrazole, 5-[4'-(bromomethyl)[1,1'-biphenyl]-2-yl]-1-(triphenylmethyl)-;Trityl tetrazole bromomethyl biphenyl;5-(4'-(BROMOMETHYL)(1,1'-BIPHENYL)-2-YL)-1-TRITYL-;5-[4'-(Bromomethyl)[1,1'-Biphenyl]-1-(Triphenylmethyl)Tetrazole]
• CAS NO: 124750-51-2
• Molecular Formula: C₃₃H₂₅BrN₄
• Molecular Weight: 557.48
• EINECS: 1592732-453-0
• Product Categories: INTERMEDIATESOF;Biphenyl & Diphenyl ether;Tetrazoles;API intermediates;(intermediates of candesartan cilexetil);Hypertension;Amines;Aromatics;Heterocycles;Intermediates
• Mol File: 124750-51-2.mol
• Article Data: 29

Chemical Properties

• Melting Point: 152-155°C
• Boiling Point: 61°C/12mmHg(lit.)
• Flash Point: 388.299 °C
• Appearance: off-white solid
• Density: 1.282 g/cm³
• Storage Temp.: -20?C Freezer
• PKA: 0.29±0.10(Predicted)
• Stability: Moisture Sensitive
• CAS DataBase Reference: 5-(4'-Bromomethyl-1,1'-biphenyl-2-yl)-1-triphenylmethyl-1H-tetrazole(CAS DataBase Reference)
• NIST Chemistry Reference: 5-(4'-Bromomethyl-1,1'-biphenyl-2-yl)-1-triphenylmethyl-1H-tetrazole(124750-51-2)
• EPA Substance Registry System: 5-(4'-Bromomethyl-1,1'-biphenyl-2-yl)-1-triphenylmethyl-1H-tetrazole(124750-51-2)

Safety Data

• RIDADR: UN 2811 6.1/PG III
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 124750-51-2(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

An intermediate in the synthesis of Losartan and Valsartan

Synthetic route

N-triphenylmethyl-5-(4'-methylbiphenyl-2-yl)tetrazole (124750-53-4) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
With bromine In hexane; water at 69℃; for 0.433333h; Temperature; Solvent; Irradiation; Flow reactor;	95.2%
With sodium bromate; sodium hydrogensulfite In water; 1,2-dichloro-ethane at 20℃; Product distribution / selectivity;	90%
With N-Bromosuccinimide; dihydrogen peroxide In dichloromethane Reflux;	88%

4'-hydroxymethyl-2-(N-trityl-1H-tetrazol-5-yl)biphenyl (154709-18-9) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
With phosphorus tribromide In dichloromethane at 10 - 20℃; for 1h;	95.07%
With sulfuric acid; potassium bromide In N,N-dimethyl acetamide at 10 - 25℃; for 7h; Reagent/catalyst; Solvent;	81.4%

N-triphenylmethyl-5-(4'-methylbiphenyl-2-yl)tetrazole (124750-53-4) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + 5-(4'-Dibromomethyl-biphenyl-2-yl)-1-trityl-1H-tetrazole

Conditions	Yield
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); sodium acetate; acetic acid In dichloromethane for 16h; Heating;	A 76% B 7%
With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; 2,2'-azobis(isobutyronitrile) In chlorobenzene at 80℃; Overall yield = 78.6 %;

salicylonitrile (611-20-1) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: 98 percent / pyridine / 1.) 0 deg C, 5 min, 2.) r.t., 25 h 2: 1.) Mg, I2; n-Bu3SnCl, 2.) Pd(PPh3)2Cl2, LiCl / 1.) THF, reflux, 30 min; THF, reflux, 20 h, 2.) DMF, 98 deg C, 24 h 3: 1.) NaN3, n-Bu3SnCl, 2.) NaOH / 1.) toluene, 115 deg C, 70 h, 2.) toluene, r.t., 3 h 4: NBS, AIBN / CCl4 / 3 h / Heating View Scheme

4-tolyl iodide (624-31-7) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) Mg, I2; n-Bu3SnCl, 2.) Pd(PPh3)2Cl2, LiCl / 1.) THF, reflux, 30 min; THF, reflux, 20 h, 2.) DMF, 98 deg C, 24 h 2: 1.) NaN3, n-Bu3SnCl, 2.) NaOH / 1.) toluene, 115 deg C, 70 h, 2.) toluene, r.t., 3 h 3: NBS, AIBN / CCl4 / 3 h / Heating View Scheme

o-cyanobromobenzene (2042-37-7) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) Mg, I2; n-Bu3SnCl, 2.) Pd(PPh3)2Cl2, LiCl / 1.) THF, reflux, 30 min; THF, reflux, 20 h, 2.) DMF, 98 deg C, 24 h 2: 1.) NaN3, n-Bu3SnCl, 2.) NaOH / 1.) toluene, 115 deg C, 70 h, 2.) toluene, r.t., 3 h 3: NBS, AIBN / CCl4 / 3 h / Heating View Scheme
Multi-step reaction with 3 steps 1: bis-triphenylphosphine-palladium(II) chloride; lithium chloride / N,N-dimethyl-formamide / Inert atmosphere 2: sodium azide; tributyltin chloride / toluene / Reflux 3: N-Bromosuccinimide; dibenzoyl peroxide / tetrachloromethane View Scheme
Multi-step reaction with 4 steps 1.1: palladium dichloride / methanol; toluene / 0.17 h / 20 °C / Inert atmosphere 1.2: 12 h / 110 °C / Inert atmosphere 2.1: zinc(II) chloride; sodium azide / N,N-dimethyl-formamide / 48 h / 120 °C 3.1: triethylamine / dichloromethane / 2 h / 0 °C / Reflux 4.1: dibenzoyl peroxide; N-Bromosuccinimide / tetrachloromethane / 3 h / Reflux View Scheme

2-Cyano-4'-methylbiphenyl (114772-53-1) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) NaN3, n-Bu3SnCl, 2.) NaOH / 1.) toluene, 115 deg C, 70 h, 2.) toluene, r.t., 3 h 2: NBS, AIBN / CCl4 / 3 h / Heating View Scheme
Multi-step reaction with 3 steps 1: sodium azide; triethylamine hydrochloride / toluene / 18 h / 105 - 110 °C 2: toluene / 3 h / 20 °C 3: N-Bromosuccinimide; dihydrogen peroxide / dichloromethane / Reflux View Scheme
Multi-step reaction with 2 steps 1: sodium azide; tributyltin chloride / toluene / Reflux 2: N-Bromosuccinimide; dibenzoyl peroxide / tetrachloromethane View Scheme

trityl chloride (76-83-5) + DL-lysine methyl ester dihydrochloride → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) NaN3, n-Bu3SnCl, 2.) NaOH / 1.) toluene, 115 deg C, 70 h, 2.) toluene, r.t., 3 h 2: NBS, AIBN / CCl4 / 3 h / Heating View Scheme

2-<(trifluoromethanesulfonyl)oxy>benzonitrile (138313-23-2) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) Mg, I2; n-Bu3SnCl, 2.) Pd(PPh3)2Cl2, LiCl / 1.) THF, reflux, 30 min; THF, reflux, 20 h, 2.) DMF, 98 deg C, 24 h 2: 1.) NaN3, n-Bu3SnCl, 2.) NaOH / 1.) toluene, 115 deg C, 70 h, 2.) toluene, r.t., 3 h 3: NBS, AIBN / CCl4 / 3 h / Heating View Scheme

2-(tetrazol-5-yl)-4'-methyl-1,1'-biphenyl (120568-11-8) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene / 3 h / 20 °C 2: N-Bromosuccinimide; dihydrogen peroxide / dichloromethane / Reflux View Scheme
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / 0 °C / Reflux 2: dibenzoyl peroxide; N-Bromosuccinimide / tetrachloromethane / 3 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: potassium hydroxide / methanol 2: bromine; acetic acid View Scheme

tributyl(p-tolyl)stannane (31614-66-1) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: bis-triphenylphosphine-palladium(II) chloride; lithium chloride / N,N-dimethyl-formamide / Inert atmosphere 2: sodium azide; tributyltin chloride / toluene / Reflux 3: N-Bromosuccinimide; dibenzoyl peroxide / tetrachloromethane View Scheme

4-methylphenylboronic acid (5720-05-8) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: palladium dichloride / methanol; toluene / 0.17 h / 20 °C / Inert atmosphere 1.2: 12 h / 110 °C / Inert atmosphere 2.1: zinc(II) chloride; sodium azide / N,N-dimethyl-formamide / 48 h / 120 °C 3.1: triethylamine / dichloromethane / 2 h / 0 °C / Reflux 4.1: dibenzoyl peroxide; N-Bromosuccinimide / tetrachloromethane / 3 h / Reflux View Scheme
Multi-step reaction with 4 steps 1: palladium diacetate; triethylamine; triphenylphosphine / acetonitrile 2: sodium azide / N,N-dimethyl-formamide 3: potassium hydroxide / methanol 4: bromine; acetic acid View Scheme
Multi-step reaction with 4 steps 1: palladium diacetate; triphenylphosphine / acetonitrile 2: sodium azide / N,N-dimethyl-formamide 3: potassium hydroxide / methanol 4: bromine; acetic acid View Scheme

o-tolylbenzoic acid (7148-03-0) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 6 steps 1: thionyl chloride 2: sodium hydroxide 3: trimethylsilylazide; diethylazodicarboxylate; triphenylphosphine 4: sodium hydroxide / tetrahydrofuran; methanol 5: N-ethyl-N,N-diisopropylamine 6: N-Bromosuccinimide / tetrachloromethane View Scheme

4'-methylbiphenyl-2-carboxylic acid chloride (114772-35-9) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 5 steps 1: sodium hydroxide 2: trimethylsilylazide; diethylazodicarboxylate; triphenylphosphine 3: sodium hydroxide / tetrahydrofuran; methanol 4: N-ethyl-N,N-diisopropylamine 5: N-Bromosuccinimide / tetrachloromethane View Scheme

N-(2-cyanoethyl)-4'-methyl[1,1']biphenyl-2-carboxamide (120568-15-2) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: trimethylsilylazide; diethylazodicarboxylate; triphenylphosphine 2: sodium hydroxide / tetrahydrofuran; methanol 3: N-ethyl-N,N-diisopropylamine 4: N-Bromosuccinimide / tetrachloromethane View Scheme

5-<4'-Methyl-1,1'-biphenyl-2-yl>-1H-tetrazole-1-propanenitrile (120568-17-4) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide / tetrahydrofuran; methanol 2: N-ethyl-N,N-diisopropylamine 3: N-Bromosuccinimide / tetrachloromethane View Scheme

C17H20N4Si → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 2 steps 2: N-Bromosuccinimide / tetrachloromethane View Scheme

C26H22Zn → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: nickel 2: toluene 4: N-Bromosuccinimide / tetrachloromethane View Scheme

para-bromotoluene (106-38-7) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 6 steps 1: magnesium / tetrahydrofuran / 2 h / 20 °C 2: tetrahydrofuran / 3 h / 20 °C 3: pyridine; trichlorophosphate / 3 h / 10 - 100 °C 4: toluene 6: N-Bromosuccinimide / tetrachloromethane View Scheme
Multi-step reaction with 9 steps 1: magnesium / tetrahydrofuran / 2 h / 20 °C 2: tetrahydrofuran / 3 h / 20 °C 3: hydrogenchloride / water 4: thionyl chloride 5: sodium hydroxide 6: trimethylsilylazide; diethylazodicarboxylate; triphenylphosphine 7: sodium hydroxide / tetrahydrofuran; methanol 8: N-ethyl-N,N-diisopropylamine 9: N-Bromosuccinimide / tetrachloromethane View Scheme

para-methylphenylmagnesium bromide (4294-57-9) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 5 steps 1: tetrahydrofuran / 3 h / 20 °C 2: pyridine; trichlorophosphate / 3 h / 10 - 100 °C 3: toluene 5: N-Bromosuccinimide / tetrachloromethane View Scheme
Multi-step reaction with 8 steps 1: tetrahydrofuran / 3 h / 20 °C 2: hydrogenchloride / water 3: thionyl chloride 4: sodium hydroxide 5: trimethylsilylazide; diethylazodicarboxylate; triphenylphosphine 6: sodium hydroxide / tetrahydrofuran; methanol 7: N-ethyl-N,N-diisopropylamine 8: N-Bromosuccinimide / tetrachloromethane View Scheme

4,4-dimethyl-2-(4'-methyl-biphenyl-2-yl)-4,5-dihydrooxazole (84392-32-5) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: pyridine; trichlorophosphate / 3 h / 10 - 100 °C 2: toluene 4: N-Bromosuccinimide / tetrachloromethane View Scheme
Multi-step reaction with 7 steps 1: hydrogenchloride / water 2: thionyl chloride 3: sodium hydroxide 4: trimethylsilylazide; diethylazodicarboxylate; triphenylphosphine 5: sodium hydroxide / tetrahydrofuran; methanol 6: N-ethyl-N,N-diisopropylamine 7: N-Bromosuccinimide / tetrachloromethane View Scheme

4'-(hydroxymethyl)-[1,1'-biphenyl]-2-carbonitrile (154709-19-0) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: zinc(II) chloride; sodium azide / butan-1-ol / 20 h / 100 - 105 °C 2.1: triethylamine / dichloromethane / 10 - 15 °C 2.2: 10 °C / Reflux 3.1: potassium bromide; sulfuric acid / N,N-dimethyl acetamide / 7 h / 10 - 25 °C View Scheme

biphenyl-2-carbonitrile (24973-49-7) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: zinc(II) chloride; hydrogenchloride / 1,2-dimethoxyethane; water / 0 - 5 °C 2.1: zinc(II) chloride; sodium azide / butan-1-ol / 20 h / 100 - 105 °C 3.1: triethylamine / dichloromethane / 10 - 15 °C 3.2: 10 °C / Reflux 4.1: potassium bromide; sulfuric acid / N,N-dimethyl acetamide / 7 h / 10 - 25 °C View Scheme

C35H28N4O2 → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrogenchloride / tetrahydrofuran; water / 3 h / 20 °C 2.1: sodium tetrahydroborate / methanol / 1 h / 5 - 20 °C 2.2: 0.25 h / 0 °C 3.1: phosphorus tribromide / dichloromethane / 1 h / 10 - 20 °C View Scheme

5-<2-(4'-formylbiphenylyl)>-2-(triphenylmethyl)-2H-tetrazole (155983-56-5) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium tetrahydroborate / methanol / 1 h / 5 - 20 °C 1.2: 0.25 h / 0 °C 2.1: phosphorus tribromide / dichloromethane / 1 h / 10 - 20 °C View Scheme

2-(4-chlorophenyl)-1,3-dioxolane (2403-54-5) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: magnesium; iodine / tetrahydrofuran; toluene / 5 h / Inert atmosphere; Reflux 2.1: tributyltin chloride; sodium azide / toluene; N,N-dimethyl-formamide / 48 h / Reflux 3.1: hydrogenchloride / tetrahydrofuran; water / 3 h / 20 °C 4.1: sodium tetrahydroborate / methanol / 1 h / 5 - 20 °C 4.2: 0.25 h / 0 °C 5.1: phosphorus tribromide / dichloromethane / 1 h / 10 - 20 °C View Scheme

2-Chlorobenzonitrile (873-32-5) → N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: magnesium; iodine / tetrahydrofuran; toluene / 5 h / Inert atmosphere; Reflux 2.1: tributyltin chloride; sodium azide / toluene; N,N-dimethyl-formamide / 48 h / Reflux 3.1: hydrogenchloride / tetrahydrofuran; water / 3 h / 20 °C 4.1: sodium tetrahydroborate / methanol / 1 h / 5 - 20 °C 4.2: 0.25 h / 0 °C 5.1: phosphorus tribromide / dichloromethane / 1 h / 10 - 20 °C View Scheme

2-propyl-4,5-bis(methoxycarbonyl)-imidazole (124750-59-0) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 2-propyl-1-[2'-(1-triphenylmethyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-1H-imidazole-4,5-dicarboxylic acid dimethyl ester (124750-61-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl acetamide; acetone Reflux; Large scale reaction;	99%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → [2'-(N-Triphenylmethyl-tetrazol-5-yl)-biphenyl-4-yl]methyl azide (124806-66-2)

Conditions	Yield
In N-methyl-acetamide	96%
With sodium azide In N,N-dimethyl-formamide at 70℃; for 0.333333h;	96%
In dimethyl sulfoxide
With sodium azide In water; N,N-dimethyl-formamide at 20℃; for 22h;

[2'-(N-Triphenylmethyl-tetrazol-5-yl)-biphenyl-4-yl]methyl azide (124806-66-2) + 5-butyl-2,4-dihydro-4-[[2-(1-triphenylmethyl-1H-tetrazol-5-yl)-[1,1'-biphenyl]-4'-yl]methyl]-3H-1,2,4-triazol-3-one (169598-69-0) + dichloromethane (75-09-2) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 2,4-Bis[[2'-(N-trityltetrazol-5-yl)biphenyl-4-yl]methyl]-5-n-butyl-2,4-dihydro-3H-1,2,4-triazol-3-one

Conditions	Yield
In methanol	96%

L-valine benzyl ester hydrochloride (2462-34-2) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → N-[(2'-(1-triphenylmethyl-tetrazol-5-yl)biphenyl-4-yl)methyl]-(L)-valine benzyl ester phosphite

Conditions	Yield
Stage #1: L-valine benzyl ester hydrochloride With sodium hydroxide In water; ethyl acetate for 0.333333h; pH=10 - 12; Stage #2: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole In ethyl acetate at 55 - 60℃; Stage #3: With phosphonic Acid In ethyl acetate for 1h;	95%

L-valine benzyl ester hydrochloride (2462-34-2) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → N-[(2'-(1-triphenylmethyltetrazol-5-yl)biphenyl-4-yl)methyl]-(L)-valine benzyl ester phosphorous acid salt

Conditions	Yield
Stage #1: L-valine benzyl ester hydrochloride With sodium hydroxide In water pH=10 - 12; Stage #2: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole In ethyl acetate at 55 - 60℃; Stage #3: With phosphorous acid In ethyl acetate for 1h;	95%

2-(2-n-butyl-4-hydroxy-6-methylpyrimidin-5-yl)-N,N-dimethylthioacetamide + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 2-n-butyl-5-(N,N-dimethylaminothioformylmethyl)-6-methyl-3-[[2'-(N-triphenylmethyl-5-tetrazolyl)biphenyl]-4-methyl]pyrimidin-4-one (1361024-52-3)

Conditions	Yield
Stage #1: 2-(2-n-butyl-4-hydroxy-6-methylpyrimidin-5-yl)-N,N-dimethylthioacetamide With lithium hydride In hexane; N,N-dimethyl-formamide at 0℃; for 1h; Inert atmosphere; Stage #2: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole In hexane; N,N-dimethyl-formamide at 70℃; for 24h; Inert atmosphere;	95%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride → 2-n-butyl-4-spirocyclopentane-1-[(2'-(tetrazol-5-yl)biphenyl-4-yl)methyl]-2-imidazolin-5-one hydrochloride sesquihydrate

Conditions	Yield
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With potassium hydroxide; tetrabutylammomium bromide In water; toluene at 85℃; for 2h; Stage #2: With hydrogenchloride; water In toluene at 55℃; for 0.75h; Product distribution / selectivity;	94%
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With potassium hydroxide; tetrabutylammomium bromide In xylene at 85℃; for 2h; Stage #2: With hydrogenchloride; water In xylene at 55℃; for 0.75h; Product distribution / selectivity;	94%
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With sodium hydroxide; 18-crown-6 ether In xylene at 85℃; for 2 - 4h; Stage #2: With hydrogenchloride; water In xylene at 55℃; for 0.75h; Product distribution / selectivity;	94%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-5-carboxylate (144689-93-0) → 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)

Conditions	Yield
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-5-carboxylate With potassium carbonate In butanone at 60℃; for 2h; Stage #2: With N,N-dimethyl acetamide In butanone at 45℃; for 4h;	93.8%
With tetrabutylammomium bromide; potassium carbonate In acetone at 50 - 60℃; for 20h; Green chemistry;	90.7%
With potassium carbonate In acetonitrile for 7h; Heating / reflux;	89%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride → 2-butyl-3-{4-[2-(1H-tetrazol-5-yl)phenyl]benzyl}-1,3-diazaspiro[4.4]non-1-en-4-one (138402-11-6)

Conditions	Yield
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With sodium hydroxide; tetrabutylammomium bromide In water; toluene at 85℃; for 2h; Stage #2: With hydrogenchloride; water In acetone at 20℃; Stage #3: With potassium hydroxide In water; acetone Product distribution / selectivity;	92%
With potassium hydroxide; tetra(n-butyl)ammonium hydrogensulfate In water; toluene at 90℃; for 1.5h; Heating / reflux;	84.3%
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With potassium hydroxide; tetra(n-butyl)ammonium hydrogensulfate In water; toluene at 90℃; for 1.5h; Stage #2: With hydrogenchloride; water In acetone at 20℃; Stage #3: With potassium hydroxide In water; acetone Product distribution / selectivity;	84%
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With tetrabutylammomium bromide; potassium carbonate In ethyl acetate at 25 - 80℃; for 10h; Stage #2: With hydrogenchloride In methanol at 0 - 30℃; for 3.5h; Stage #3: With sodium hydroxide In water; toluene at 0 - 30℃; for 0.5h; pH=12;

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride → 2-n-butyl-4-spirocyclopentane-1-[(2'-(tetrazol-5-yl)biphenyl-4-yl)methyl]-2-imidazolin-5-one hydrochloride hemihydrate

Conditions	Yield
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With sodium hydroxide; tetrabutylammomium bromide In water; toluene at 85℃; for 2h; Stage #2: With hydrogenchloride; water In toluene at 55℃; for 0.75h; Product distribution / selectivity;	92%
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With potassium hydroxide In toluene at 85℃; for 2h; Stage #2: With hydrogenchloride; water In toluene at 55℃; for 0.75h; Product distribution / selectivity;	69%
Stage #1: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole; 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride With potassium carbonate In MIBK (methyl isobutyl ketone); water at 85℃; for 2h; Stage #2: With hydrogenchloride; water In MIBK (methyl isobutyl ketone) at 55℃; for 0.75h; Product distribution / selectivity;	69%

ethyl 2-[(N-tert-butoxycarbonyl)amino]-3-nitrobenzoate (136285-65-9) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → ethyl 2-[(N-tert-butoxycarbonyl)-[[2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl]biphenyl-4-yl]methyl]amino]-3-nitrobenzoate (906474-56-4)

Conditions	Yield
With potassium carbonate In acetonitrile for 5h; Reflux;	92%
With potassium carbonate In acetonitrile at 80℃; for 7h;

4-methoxy-aniline (104-94-9) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 4-methoxy-N-((2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methyl)aniline

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide Reflux;	92%

2-(2-thienyl)-1,3-diazaspiro[4.4]non-1-en-4-one (1199814-93-1) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 2-(2-thienyl)-3-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-1,3-diazaspiro[4.4]non-1-en-4-one (1199814-94-2)

Conditions	Yield
Stage #1: 2-(2-thienyl)-1,3-diazaspiro[4.4]non-1-en-4-one With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole In N,N-dimethyl-formamide at 20℃;	91%

N-(3-methoxy)benzyl-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide (1239196-62-3) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → N-(3-methoxy)benzyl-1-([2'-(1-triphenylmethyltetrazol-5-yl)-(1,1'-biphenyl)-4-yl]methyl)-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide (1390645-40-5)

Conditions	Yield
Stage #1: N-(3-methoxy)benzyl-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide With potassium tert-butylate In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole In N,N-dimethyl-formamide at 0 - 25℃; for 12h;	90.2%

2,2,2-trifluoroacetamide (354-38-1) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → C35H26F3N5O (868742-05-6)

Conditions	Yield
With 18-crown-6 ether; potassium tert-butylate In tetrahydrofuran; diethyl ether at 20℃; for 96h;	90%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + 2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one hydrochloride → trityl irbesartan (138402-10-5)

Conditions	Yield
In N,N-dimethyl-formamide for 0.0194444h; microwave irradiation;	90%

trityl chloride (76-83-5) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + (S)-4-isopropyl-2-(thiophen-2-yl)-4,5-dihydrooxazole (149065-76-9) → (1S)-N-(1-hydroxymethyl-2-methyl-propyl)-N'-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-thiophene-2-carboxamide (1033772-55-2)

Conditions	Yield
With potassium carbonate; potassium iodide In butanone for 24h; Product distribution / selectivity; Heating / reflux;	90%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + 2-amino-phenol (95-55-6) → 2-hydroxy-N-((2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methyl)aniline

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide Reflux;	90%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + 3-fluoro-4-(morpholinyl)aniline (93246-53-8) → 3-fluoro-4-morpholino-N-((2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-yl)methyl)aniline

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide Reflux;	90%

N-benzyl-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide (1239196-56-5) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → N-benzyl-1-([2'-(1-triphenylmethyltetrazol-5-yl)-(1,1'-biphenyl)-4-yl]methyl)-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide (1390645-39-2)

Conditions	Yield
Stage #1: N-benzyl-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide With potassium tert-butylate In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole In N,N-dimethyl-formamide at 0 - 25℃; for 12h;	89.7%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + ethyl 4-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-5-carboxylate (144689-93-0) → 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-(1-hydroxy-1-methylethyl)-2-propyl-1-(4-(2-(1-(triphenylmethyl)tetrazol-5-yl)phenyl)phenyl)methylimidazole-5-carboxylic acid (761404-85-7) + C45H42N6O2

Conditions	Yield
With potassium phosphate In N,N-dimethyl acetamide at 60 - 65℃; for 6h; Solvent; Reagent/catalyst;	A 89.6% B 0.02% C 0.02%

p-toluidine (106-49-0) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 4-methyl-N-((2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methyl)aniline

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide Reflux;	89%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + (4-acetyl-5-methyl-1-pentanoylamino-1H-pyrrol-2-yl)-acetic acid ethyl ester (230627-21-1) → (4-acetyl-5-methyl-1-{pentanoyl-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-amino}-1H-pyrrol-2-yl)-acetic acid ethyl ester (230627-26-6)

Conditions	Yield
With sodium hydroxide In dichloromethane at 20℃; Alkylation;	88.7%

1H-Naphtho<2,3-d><1,2,3>triazole (269-12-5) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 1-[2'-(1-triphenylmethyl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-1H-naphtho[2,3-d][1,2,3]triazole (194417-18-0)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 0℃; 1.) 1h, 2.) 0 deg C, 4 h; r.t., overnight;	88%

4-amino-benzoic acid (150-13-0) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 4-carboxy-N-((2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl)methyl)aniline

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide Reflux;	88%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) + N-butylamine (109-73-9) → 1-trityl-5-(4'-butylaminomethyl-1,1'-biphenyl-2-yl)-1H-tetrazole

Conditions	Yield
In tetrahydrofuran at 20℃; for 3h;	88%
In tetrahydrofuran at 20℃; for 2h;	80%

N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → 5-(4'-(chloromethyl)-[1,1'-biphenyl]-2-yl)-1H-tetrazole

Conditions	Yield
With hydrogenchloride In water; ethyl acetate at 80℃; for 15h; Temperature; Solvent;	88%

N-(4-methoxy)benzyl-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide (1239196-65-6) + N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole (124750-51-2) → N-(4-methoxy)benzyl-1-([2'-(1-triphenylmethyltetrazol-5-yl)-(1,1'-biphenyl)-4-yl]methyl)-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide (1390645-41-6)

Conditions	Yield
Stage #1: N-(4-methoxy)benzyl-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide With potassium tert-butylate In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: N-(triephenylmethyl)-5-<4'-(bromomethyl)-biphenyl-2-yl>tetrazole In N,N-dimethyl-formamide at 0 - 25℃; for 12h;	87.7%

Upstream product

• 2042-37-7 o-cyanobromobenzene 
• 120568-11-8 2-(tetrazol-5-yl)-4'-methyl-1,1'-biphenyl 
• 154709-19-0 4'-(hydroxymethyl)-[1,1'-biphenyl]-2-carbonitrile 
• 24973-49-7 biphenyl-2-carbonitrile 
• 154709-18-9 4'-hydroxymethyl-2-(N-trityl-1H-tetrazol-5-yl)biphenyl 
• 76-83-5 trityl chloride 
• 114772-53-1 2-Cyano-4'-methylbiphenyl 
• 400747-06-0 C₁₆H₁₃O₂N 
• 873-32-5 2-Chlorobenzonitrile 
• 2403-54-5 2-(4-chlorophenyl)-1,3-dioxolane 
• 155983-56-5 5-<2-(4'-formylbiphenylyl)>-2-(triphenylmethyl)-2H-tetrazole 
• 84392-32-5 4,4-dimethyl-2-(4'-methyl-biphenyl-2-yl)-4,5-dihydrooxazole 
• 4294-57-9 para-methylphenylmagnesium bromide 
• 106-38-7 para-bromotoluene 

Downstream Products

• 135015-78-0 2-Ethyl-7-methoxy-4-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methoxy]quinoline hydrochloride 
• 135015-77-9 7-Cyano-2-ethyl-4-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methoxy]quinoline hydrochloride 
• 143494-86-4 5-Cyano-2-ethyl-4-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methoxy]quinoline hydrochloride 
• 175473-51-5 5-[4'-(3-Butyl-[1,2,4]oxadiazol-5-ylsulfanylmethyl)-biphenyl-2-yl]-1-trityl-1H-tetrazole 
• 175473-44-6 4-Butyl-3-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-3H-[1,2,3,5]oxathiadiazole 2-oxide 
• 175473-37-7 3-Butyl-4-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4H-[1,2,4]oxadiazol-5-one 
• 175473-46-8 4-Pentyl-3-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-3H-[1,2,3,5]oxathiadiazole 2-oxide 
• 175473-65-1 4-Butyl-2-phenyl-5-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-2,5-dihydro-[1,2,3,5]thiatriazole 1-oxide 
• 175473-69-5 4-Butyl-2-m-tolyl-5-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-2,5-dihydro-[1,2,3,5]thiatriazole 1-oxide 
• 175473-70-8 4-Butyl-2-p-tolyl-5-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-2,5-dihydro-[1,2,3,5]thiatriazole 1-oxide 
• 175473-66-2 4-Butyl-2-(2-ethyl-phenyl)-5-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-2,5-dihydro-[1,2,3,5]thiatriazole 1-oxide 
• 175473-68-4 4-Butyl-2-o-tolyl-5-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-2,5-dihydro-[1,2,3,5]thiatriazole 1-oxide 
• 175473-67-3 4-Butyl-2-(2-trifluoromethyl-phenyl)-5-[2'-(1-trityl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-2,5-dihydro-[1,2,3,5]thiatriazole 1-oxide 
• 194417-18-0 1-[2'-(1-triphenylmethyl-1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-1H-naphtho[2,3-d][1,2,3]triazole 

Relevant articles and documents

Method for synthesizing high-purity sartan side chain TTBB

The invention discloses a method for synthesizing high-purity sartan side chain TTBB. The method comprises the following steps: taking 4-methyl-2-cyanobiphenyl as a starting material; under a catalytic action of lewis acid triethylamine hydrochloride, carrying out cyclization reaction on the 4-methyl-2-cyanobiphenyl and sodium azide to generate a 5-[2-(4'-methyldiphenyl)]tetrazole compound; reacting the 5-[2-(4'-methyldiphenyl)] tetrazole compound with triphenylchloromethane under an alkaline condition to generate an N-(triphenylmethyl)-5-(4'-methylbiphenyl-2-yl)tetrazole compound; reacting togenerate a mixture of a compound TTBB and a compound Br-TTBB under the action of bromine-containing substances; promoting the compound Br-TTBB to be converted into the compound TTBB under the actionof diethyl phosphite by the mixture, thus finally obtaining the high-purity sartan side chain TTBB. The synthetic process disclosed by the invention has the advantages of better economical property, environment friendliness, high efficiency, simplicity and convenience; the mode of improving the purity of a target product through recrystallization for multiple times by adopting a conventional method is avoided.

1,(3,)5-substituted imidazoles, useful in the treatment of hypertension and methods for their preparation

The present invention provides novel 1,5 and 1,3,5-substituted imidazole compounds in hydrophilic or lipophilic form, which are useful as angiotensin II ATI receptor antagonists suitable for transdermal delivery. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing compounds and their use in methods of treating hypertension and cardiovascular diseases.

A process for the preparation of olmesartan

The invention discloses a preparation method of Olmesartan Medoxomil. The method is used for synthesizing an important intermediate 4-[2-(2-triphenylmethyl tetrazole-5-yl) phenyl] benzyl bromide (a compound III) so as to prepare the compound Olmesartan Medoxomil. The method is high in yield, easy to separate and purify, simple to operate and suitable for industrial production.