398489-26-4

Basic information

• Product Name: tert-Butyl 3-oxoazetidine-1-carboxylate
• Synonyms: 1-BOC-3-AZETIDINONE;3-OXO-AZETIDINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER;3-OXOAZETIDINE, N-BOC PROTECTED;TERT-BUTYL 3-OXOAZETIDINE-1-CARBOXYLATE;1-Boc-azetidin-3-one;1-TERT-BUTOXYCARBONYL-3-AZETIDINONE;1-N-Boc-3-azetidinone;3-Oxoazetidine, N-BOC protected 95%
• CAS NO: 398489-26-4
• Molecular Formula: C₈H₁₃NO₃
• Molecular Weight: 171.19
• EINECS: 1592732-453-0
• Product Categories: pharmacetical;Heterocycles series;Azetidine;Ring Systems;Amines;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;pharmaceutical and biochemical
• Mol File: 398489-26-4.mol
• Article Data: 37

Chemical Properties

• Melting Point: 49-52°C
• Boiling Point: 251.3 °C at 760 mmHg
• Flash Point: 102 °C
• Appearance: White to off-white/Crystalline Powder
• Density: 1.174 g/cm³
• Vapor Pressure: 0.0369mmHg at 25°C
• Storage Temp.: Store under inert gas
• PKA: -1.99±0.20(Predicted)
• Sensitive: Moisture Sensitive/Stench
• CAS DataBase Reference: tert-Butyl 3-oxoazetidine-1-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: tert-Butyl 3-oxoazetidine-1-carboxylate(398489-26-4)
• EPA Substance Registry System: tert-Butyl 3-oxoazetidine-1-carboxylate(398489-26-4)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 22-37/38-41
• Safety Statements: 26-39
• RIDADR: UN 3335
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 398489-26-4(Hazardous Substances Data)

Usage

Chemical Properties

White to light brown solid

Uses

1-Boc-3-azetidinone can be used for the preparation of antibacterial aminoglycoside analogs.

General Description

tert-Butyl 3-oxoazetidine-1-carboxylate is moisture sensitive and incompatible with oxidizing agents. This chemical can cause skin irritation and severe eye irritation.

InChI:InChI=1/C6H14N2.2ClH/c1-8-4-2-3-6(7)5-8;;/h6H,2-5,7H2,1H3;2*1H

Synthetic route

tert-butyl 3-hydroxyazetidine-1-carboxylate (141699-55-0) → tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4)

Conditions	Yield
With tetrapropylammonium perruthennate; 4-methylmorpholine N-oxide In acetonitrile at 0 - 20℃; for 18h; Inert atmosphere; Molecular sieve;	99%
With 1-methyl-1H-imidazole; tetrakis(acetonitrile)copper(I) trifluoromethanesulfonate; 4,4'-Dimethoxy-2,2'-bipyridin; 9-azabicyclo[3.3.1]nonane N-oxyl; oxygen In acetonitrile at 20℃; for 0.5h; Time;	98%
With pyridine-SO3 complex; triethylamine In dimethyl sulfoxide at 10 - 20℃; Inert atmosphere;	95%

1,3-dibromoacetone ethylene glycol (20599-01-3) + tert-butyl carbamate (4248-19-5) → tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4)

Conditions	Yield
With sodium carbonate In 1,4-dioxane at 50℃; for 16h; Reagent/catalyst; Solvent; Temperature;	92%

1-tert-butoxycarbonyl-3,3-dimethoxyazetidine → tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4)

Conditions	Yield
With citric acid In water; ethyl acetate at 20 - 40℃;	85.4%

di-tert-butyl dicarbonate (24424-99-5) + 3,3-dimethoxyazetidine → tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4)

Conditions	Yield
With triethylamine In dichloromethane at 10 - 40℃;	80.2%

di-tert-butyl dicarbonate (24424-99-5) → tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / tetrahydrofuran / 1 h / 20 °C 2: triethylamine / sulfur trioxide pyridine complex / chloroform; dimethyl sulfoxide / 4 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / 1,4-dioxane; water / 15 h / 20 °C 2: oxalyl dichloride; dimethyl sulfoxide; triethylamine / dichloromethane / 15 h / -78 - 20 °C View Scheme
Multi-step reaction with 2 steps 1: triethylamine / ethanol / 16 h / 0 - 20 °C 2: pyridine-SO3 complex; triethylamine / dimethyl sulfoxide / 10 - 20 °C / Inert atmosphere View Scheme

tert-butyl 3-hydroxyazetidine-1-carboxylate (141699-55-0) → tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + 1,1-dimethylethyl 5-oxo-3-oxazolidinecarboxylate (172096-95-6)

Conditions	Yield
With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium hydrogencarbonate; potassium bromide In dichloromethane; water at -10 - -5℃; Temperature;

methylene-carbamic acid tert-butyl ester (801290-71-1) → tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: trichlorophosphate / diethyl ether / Inert atmosphere; Schlenk technique; Reflux 2: zinc; acetic acid / 7 h / 20 - 80 °C / Inert atmosphere; Schlenk technique View Scheme

C8H11Cl2NO3 → tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4)

Conditions	Yield
With acetic acid; zinc at 20 - 80℃; for 7h; Inert atmosphere; Schlenk technique;

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + dimethyl amine (124-40-3) → tert-butyl 3-(dimethylamino)azetidine-1-carboxylate (792970-55-9)

Conditions	Yield
Stage #1: tert-butyl 3-oxoazetidine-1-carboxylate; dimethyl amine With hydrogen; acetic acid; palladium 10% on activated carbon In tetrahydrofuran; methanol at 20℃; for 14h; Stage #2: With sodium hydrogencarbonate In water; ethyl acetate	100%

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + Methyltriphenylphosphonium bromide (1779-49-3) → 3-methylene-azetidine-1-carboxylic acid tert-butyl ester (934664-41-2)

Conditions	Yield
Stage #1: potassium tert-butylate; Methyltriphenylphosphonium bromide In diethyl ether at 20℃; for 1h; Stage #2: tert-butyl 3-oxoazetidine-1-carboxylate In diethyl ether at 35℃; for 2h;	100%
Stage #1: Methyltriphenylphosphonium bromide With potassium tert-butylate In diethyl ether at 20℃; for 1h; Stage #2: tert-butyl 3-oxoazetidine-1-carboxylate In diethyl ether at 35℃; for 2h;	100%
Stage #1: Methyltriphenylphosphonium bromide With potassium tert-butylate In diethyl ether at 20℃; for 1h; Stage #2: tert-butyl 3-oxoazetidine-1-carboxylate In diethyl ether at 35℃; for 2h;	100%

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + (triphenylphosphoranylidene)acetaldehyde (2136-75-6) → tert-butyl 3-(2-oxomethylene)azetidine-1-carboxylic acid (1223573-23-6)

Conditions	Yield
In dichloromethane at 40℃; for 6h;	100%
In dichloromethane at 40℃; for 6h;	100%
In dichloromethane at 40℃;	99%

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + vinyl magnesium bromide (1826-67-1) → tert-butyl 3-hydroxy-3-vinylazetidine-1-carboxylate (398489-51-5)

Conditions	Yield
In tetrahydrofuran at -78℃; for 1h; Inert atmosphere;	100%
In tetrahydrofuran at -20℃; for 0.5h; Inert atmosphere;	99%
In tetrahydrofuran at -30℃; for 2h; Inert atmosphere;

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + ethyl (triphenylphosphoranylidene)acetate (1099-45-2) → tert-butyl 3-(2-ethoxy-2-oxoethylidene)azetidine-1-carboxylate (1002355-96-5)

Conditions	Yield
In dichloromethane for 6h; Wittig Olefination; Inert atmosphere; Schlenk technique; Reflux;	100%
In dichloromethane at 40℃; for 4h; Cooling with ice;	100%
In dichloromethane at 40℃; for 4.25h; Cooling with ice;	100%

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + tert-butyl diethylphosphonoacetate (27784-76-5) → tert-butyl 3-(2-(tert-butoxy)-2-oxoethylidene)azetidine-1-carboxylate

Conditions	Yield
Stage #1: tert-butyl diethylphosphonoacetate With potassium tert-butylate In tetrahydrofuran at 0 - 20℃; Stage #2: tert-butyl 3-oxoazetidine-1-carboxylate In tetrahydrofuran at 0 - 20℃;	100%

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + (carbobenzyloxymethylene)triphenylphosphorane (15097-38-8) → tert-butyl 3-(2-benzyloxy-2-oxo-ethylidene)azetidine-1-carboxylic acid

Conditions	Yield
In toluene for 2h; Reflux;	100%

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + (S)-1-amino-2-(methoxymethyl)pyrrolidine (59983-39-0) → C14H25N3O3

Conditions	Yield
at 55℃; for 16h;	100%

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + 5-bromo-2,3-dihydro-1H-isoindole hydrochloride (919346-89-7) → tert-butyl-3-(5-bromoisoindolin-2-yl)azetidine-1-carboxylate

Conditions	Yield
With acetic acid In methanol at 50℃; for 16h;	100%

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + diethyl 1-cyanomethylphosphonate (2537-48-6) → 3-(cyanomethylene)azetidine-1-carboxylic acid tert-butyl ester (1153949-11-1)

Conditions	Yield
Stage #1: diethyl 1-cyanomethylphosphonate With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; Stage #2: tert-butyl 3-oxoazetidine-1-carboxylate In tetrahydrofuran; mineral oil Product distribution / selectivity;	99%
Stage #1: diethyl 1-cyanomethylphosphonate With sodium hydride In tetrahydrofuran at 0 - 20℃; Stage #2: tert-butyl 3-oxoazetidine-1-carboxylate In tetrahydrofuran at 0℃; Stage #3: With water In tetrahydrofuran	98%
Stage #1: diethyl 1-cyanomethylphosphonate With potassium tert-butylate In tetrahydrofuran at 0 - 30℃; Stage #2: tert-butyl 3-oxoazetidine-1-carboxylate In tetrahydrofuran at 0 - 30℃;	95%

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + methylmagnesium chloride (676-58-4) → tert-butyl 3-hydroxy-3-methylazetidine-1-carboxylate (1104083-23-9)

Conditions	Yield
Stage #1: tert-butyl 3-oxoazetidine-1-carboxylate; methylmagnesium chloride In tetrahydrofuran at 0℃; for 1h; Stage #2: With water; ammonium chloride In tetrahydrofuran	99%
Stage #1: tert-butyl 3-oxoazetidine-1-carboxylate; methylmagnesium chloride In tetrahydrofuran at 0 - 20℃; for 6h; Stage #2: With water; ammonium chloride In tetrahydrofuran at 0℃; for 0.166667h;

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) → tert-butyl 3-hydroxyazetidine-1-carboxylate (141699-55-0)

Conditions	Yield
With sodium tetrahydroborate; ethanol for 2h;	99%
With sodium tetrahydroborate In tetrahydrofuran at 20℃; for 6h;	84%
With methanol; sodium tetrahydroborate at 0 - 20℃; for 1h;

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) → 3-methylene-azetidine-1-carboxylic acid tert-butyl ester (934664-41-2)

Conditions	Yield
With potassium tert-butylate; methyl-triphenylphosphonium iodide In diethyl ether at 35℃; for 2h;	99%

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + 1-triphenylphosphoranylidene-2-propanone (1439-36-7) → tert-butyl 3-acetonylideneazetidine-1-carboxylate

Conditions	Yield
In toluene at 70℃; for 2h;	99%

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + nitromethane (75-52-5) → 3-hydroxy-3-(nitromethyl)azetidin-1-carboxylic acid tert-butyl ester (1008526-70-2)

Conditions	Yield
With triethylamine In ethanol at 20℃; for 16h; Inert atmosphere;	98%
With triethylamine In ethanol at 20℃; for 16h;	98%
triethylamine In ethanol for 18h;	97%

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + 4-methoxybenzenesulfonyl hydrazide (1950-68-1) → tert-butyl 3-(2-((4-methoxyphenyl)sulfonyl)hydrazineylidene)azetidine-1-carboxylate (1510865-67-4)

Conditions	Yield
In toluene for 2h; Reflux;	98%
In dimethylsulfoxide-d6 at 60℃; Schlenk technique;	73%

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + methyl iodide (74-88-4) → tert-butyl 3-methoxyazetidine-1-carboxylate (429669-07-8)

Conditions	Yield
Stage #1: tert-butyl 3-oxoazetidine-1-carboxylate With sodium hydride In tetrahydrofuran at 0 - 20℃; for 1h; Inert atmosphere; Stage #2: methyl iodide In tetrahydrofuran at 20℃; for 2h; Inert atmosphere;	98%

azetidine (503-29-7) + tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) → tert-butyl [1,3'-biazetidine]-1'-carboxylate

Conditions	Yield
Stage #1: azetidine; tert-butyl 3-oxoazetidine-1-carboxylate With acetic acid In 1,2-dichloro-ethane at 20℃; Stage #2: With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane for 4h;	98%

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + ethylmagnesium bromide (925-90-6) → tert-butyl 3-ethyl-3-hydroxyazetidine-1-carboxylate (398489-28-6)

Conditions	Yield
In tetrahydrofuran at 0 - 20℃; for 5h; Inert atmosphere;	98%

tert-butyl 3-oxoazetidine-1-carboxylate (398489-26-4) + 4-Octyne (1942-45-6) → tert-butyl 3-oxo-4,5-dipropyl-3,6-dihydropyridine-1(2H)-carboxylate (1372173-47-1)

Conditions	Yield
With bis(1,5-cyclooctadiene)nickel (0); triphenylphosphine In toluene at 60℃; for 6h; Inert atmosphere; regioselective reaction;	97%
With bis(1,5-cyclooctadiene)nickel (0); triphenylphosphine In toluene at 60℃; for 6h; Glovebox; Inert atmosphere;	97%
With bis(triphenylphosphine)nickel(II) chloride; zinc In acetonitrile at 60℃; for 16h; Catalytic behavior; Reagent/catalyst; Solvent; Schlenk technique; Inert atmosphere;	95%

Upstream product

• 144-55-8 sodium hydrogencarbonate 
• 801290-71-1 methylene-carbamic acid tert-butyl ester 
• 24424-99-5 di-tert-butyl dicarbonate 
• 20599-01-3 2,2-bis(bromomethyl)-1,3-dioxolane 
• 4248-19-5 tert-butyl carbazate 
• 141699-55-0 tert-butyl 3-hydroxyazetidine-1-carboxylate 

Downstream Products

• 958297-39-7 3-phenylazetidin-3-ol trifluoroacetate 
• 958297-44-4 tert-butyl 3-(4-fluorophenyl)-3-hydroxyazetidine-1-carboxylate 
• 934665-46-0 1,1-dimethylethyl 3-ethylideneazetidine-1-carboxylate 
• 1143582-51-7 C₂₁H₃₃N₃O₂ 
• 1258557-18-4 3-[2-({2-[(1-methyl-1H-pyrazol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl}amino)phenyl]azetidin-3-ol 
• 1196733-65-9 C₁₈H₂₈N₂O₃ 
• 1035351-06-4 1-[(tert-butoxy)carbonyl]-3-hydroxyazetidine-3-carboxylic acid 
• 1346507-95-6 tert-butyl 3-((1R,2S,3S,4R,5S)-4-((2R,3R,6S)-6-((tert-butoxycarbonyl(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)amino)methyl)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-2-yloxy)-2-((2R,3R,4R,5R)-4-(tert-butoxycarbonyl(methyl)amino)-3,5-dihydroxy-5-methyltetrahydro-2H-pyran-2-yloxy)-5-(tert-butoxycarbonylamino)-3-hydroxycyclohexylcarbamoyl)-3-hydroxyazetidine-1-carboxylate 
• 1422035-95-7 1,3-di-tert-butyl 2-(2-{[1-(tert-butoxycarbonyl)azetidine-3-yl]amino}phenyl)propanedioate 
• 1451998-23-4 tert-butyl 3-methoxy-3-phenylazetidine-1-carboxylate 
• 1451998-27-8 tert-butyl 3-((methylsulfonyl)oxy)-3-phenylazetidine-1-carboxylate 
• 1451998-28-9 tert-butyl 3-azido-3-phenylazetidine-1-carboxylate 
• 1451998-31-4 tert-butyl 3-(3-bromophenyl)-3-fluoroazetidine-1-carboxylate 
• 1451998-32-5 tert-butyl 3-fluoro-3-(3-(pyridin-4-yl)phenyl)azetidine-1-carboxylate 

Relevant articles and documents

PROCESSES OF PREPARING A JAK1 INHIBITOR

The present application provides processes for preparing 4-[3-(cyanomethyl)-3-(3′,5′-dimethyl-1H, 1′H-4,4′-bipyrazol-1-yl)azetidin-1-yl]-2,5-difluoro-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide, and phosphoric acid salt thereof, which is useful as a selective (Janus kinase 1) JAK1 inhibitor, as well as salt forms and intermediates related thereto.

Synthesis of trisubstituted alkenes by Ni-catalyzed hydroalkylation of internal alkynes with cycloketone oxime esters

A method for Ni-catalyzed hydroalkylation of internal alkynes with cycloketone oxime esters was developed. The reaction has a broad substrate scope. This hydroalkylation shows excellent regio-and stereo-selectivity. This method enables readily available starting materials to be used to access a range of cyano-substituted single-configuration trisubstituted alkenes. These are valuable feedstock chemicals and are widely used in synthetic and medicinal chemistry.

Preparation method of 3-oxazetidine-1-carboxylic acid tert-butyl ester

The invention discloses a preparation method of 3-oxaazetidine-1-carboxylic acid tert-butyl ester. The preparation method comprises the following steps: firstly, synthesizing 2,2-bis(bromomethyl)-1,3-dioxolane from 1,3-dibromoacetone and ethylene glycol under the action of an acid, and cyclizing the 2,2-bis(bromomethyl)-1,3-dioxolane and tert-butyl carbamate under the action of an alkali to generate the 3-oxazetidine-1-carboxylic acid tert-butyl ester. The raw materials adopted in the method are cheap and easy to obtain, and the method is simple to operate, mild in reaction conditions, low inequipment requirements and suitable for industrial large-scale production.