4515-23-5

Basic information

• Product Name: N-CARBOBENZYLOXY-L-ASPARTIC ANHYDRIDE
• Synonyms: N-CARBOBENZYLOXY-L-ASPARTIC ANHYDRIDE;N-CBZ-L-ASPARTIC ANHYDRIDE;(S)-2-BENZYLOXYCARBAMYLSUCCINIC ANHYDRIDE;(S)-benzyl (tetrahydro-2,5-dioxo-3-furyl)carbamate;N-Z-L-aspartic anhydride, 95%;Carbamic acid, [(3S)-tetrahydro-2,5-dioxo-3-furanyl]-, phenylmethyl ester (9CI);(2,5-Dioxotetrahydrofuran-3β-yl)carbamic acid benzyl ester;(2S)-2-(Benzyloxycarbonylamino)succinic anhydride
• CAS NO: 4515-23-5
• Molecular Formula: C₁₂H₁₁NO₅
• Molecular Weight: 249.22
• EINECS: 224-838-3
• Product Categories: N-CBZ;Aspartic Acid Derivatives;Peptide Synthesis;Unnatural Amino Acid Derivatives
• Mol File: 4515-23-5.mol
• Article Data: 22

Chemical Properties

• Melting Point: 123-124 °C(lit.)
• Boiling Point: 490℃
• Flash Point: 250℃
• Appearance: White Powder
• Density: 1.37
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.573
• Storage Temp.: 2-8°C
• PKA: 9.93±0.20(Predicted)
• CAS DataBase Reference: N-CARBOBENZYLOXY-L-ASPARTIC ANHYDRIDE(CAS DataBase Reference)
• NIST Chemistry Reference: N-CARBOBENZYLOXY-L-ASPARTIC ANHYDRIDE(4515-23-5)
• EPA Substance Registry System: N-CARBOBENZYLOXY-L-ASPARTIC ANHYDRIDE(4515-23-5)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 4515-23-5(Hazardous Substances Data)

Usage

General Description

N-Carbobenzyloxy-L-aspartic anhydride is a chemical compound commonly used in organic synthesis and peptide chemistry. It is a reactive intermediate that can be used to protect the carboxyl group of amino acids during solid-phase peptide synthesis. It is also used as a reagent to create esters and amides of aspartic acid derivatives. N-CARBOBENZYLOXY-L-ASPARTIC ANHYDRIDE is considered hazardous and should be handled with caution due to its potential to cause skin and eye irritation, as well as respiratory and digestive tract irritation if inhaled or ingested. Overall, N-Carbobenzyloxy-L-aspartic anhydride plays an important role in the preparation and modification of peptides and amino acid derivatives in organic chemistry.

InChI:InChI=1/C12H11NO5/c14-10-6-9(11(15)18-10)13-12(16)17-7-8-4-2-1-3-5-8/h1-5,9H,6-7H2,(H,13,16)/t9-/m0/s1

Synthetic route

N-Cbz-L-Asp (1152-61-0) → N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5)

Conditions	Yield
	100%
With dicyclohexyl-carbodiimide In ethyl acetate 1.) 1 h, 0 deg C, 2.) 24 h, r.t.;	98%
With acetic anhydride for 0.0166667h; microwave irradiation;	98%

N-Cbz-L-Asp (1152-61-0) → benzyl N-[(3R)-2,5-dioxotetrahydrofuran-3-yl]carbamate (75443-62-8) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5)

Conditions	Yield
With acetic anhydride at 20 - 45℃; for 2.25h; Product distribution; Further Variations:; Reagents; Solvents; Temperatures;

benzyl chloroformate (501-53-1) → N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 89 percent 2: 98 percent / dicyclohexylcarbodiimide / ethyl acetate / 1.) 1 h, 0 deg C, 2.) 24 h, r.t. View Scheme
Multi-step reaction with 2 steps 1: K2CO3 / H2O / Ambient temperature 2: Ac2O / acetic acid / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: K2CO3 / H2O 2: Ac2O / acetic acid View Scheme

benzyl alcohol (100-51-6) → N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: toluene / anfangs unter Kuehlung 2: MgO; water; diethyl ether 3: acetic acid anhydride View Scheme

n-Dodecylamine (124-22-1) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → N-dodecyl-2-carbobenzyloxyaminosuccinamic acid

Conditions	Yield
With triethylamine In dichloromethane for 12h;	97%
With triethylamine In dichloromethane for 12h;	97%

N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → benzyl (3S)-5-oxotetrahydro-3-furanylcarbamate (87219-29-2)

Conditions	Yield
With sodium tetrahydroborate In tetrahydrofuran	91%
With sodium tetrahydroborate at 0℃; for 3h;	91%
With sodium tetrahydroborate	86%

aniline (62-53-3) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → benzyloxycarbonyl-L-aspartic acid dianilide (685139-81-5)

Conditions	Yield
Stage #1: N-benzyloxycarbonyl-L-aspartic acid anhydride In dimethyl sulfoxide at 20℃; for 3h; Stage #2: aniline With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide at 20℃; for 24h;	87%
Stage #1: N-benzyloxycarbonyl-L-aspartic acid anhydride In N,N-dimethyl-formamide at 20℃; for 3h; Stage #2: aniline With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide at 20℃; for 24h;	87%

3-methyl-1,2,4-thiadiazol-5-amine (17467-35-5) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → 2-benzyloxycarbonylamino-N-(3-methyl-[1,2,4]thiadiazol-5-yl)-succinamic acid (403736-43-6)

Conditions	Yield
In dimethyl sulfoxide at 20℃; for 2h;	85%

benzyl alcohol (100-51-6) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → Z-Asp-OBn (4779-31-1)

Conditions	Yield
at 90℃; for 3.5h;	82%
at 90℃; for 3.5h;	72%

ethanol (64-17-5) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → (S)-3-(benzyloxycarbonylamino)-4-ethoxy-4-oxobutanoic acid (4668-43-3)

Conditions	Yield
at 20℃; for 36h;	81%
Heating;
With N-cyclohexyl-cyclohexanamine In diethyl ether
for 18h; Product distribution / selectivity; Heating / reflux;

3,4-dimethoxyaniline (6315-89-5) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → [1,2-bis-(3,4-dimethoxy-phenylcarbamoyl)-ethyl]-carbamic acid benzyl ester (932743-84-5)

Conditions	Yield
With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide at 20℃; for 24h;	79%

N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → (3S)-benzyl N-(1-hydroxy-2,5-dioxo-pyrrolidin-3-yl)carbamate

Conditions	Yield
Stage #1: N-benzyloxycarbonyl-L-aspartic acid anhydride With sodium hydroxide; hydroxylamine hydrochloride In 1,4-dioxane; water at 19.85 - 49.85℃; for 1.25h; Stage #2: at 124.85℃; for 0.333333h;	77%
With sodium hydroxide; hydroxylamine hydrochloride In 1,4-dioxane; water at 60℃; for 2h;	75%
With hydroxylamine hydrochloride; sodium carbonate In water at 0℃; for 1h;	54%

benzylamine (100-46-9) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → (S)-(1-benzyl-2,5-dioxo-pyrrolidin-3-yl)carbamic acid benzyl ester (124166-11-6)

Conditions	Yield
toluene-4-sulfonic acid In DMF (N,N-dimethyl-formamide); toluene at 22 - 110℃; for 31h; Heating / reflux; Azeotropic dehydratation;	77%
toluene-4-sulfonic acid In DMF (N,N-dimethyl-formamide); toluene at 30 - 110℃; for 25h; Heating / reflux;	n/a
In ethanol at 20℃; for 18h;	n/a

4-tert-Butylaniline (769-92-6) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → [1,2-bis-(4-tert-butyl-phenylcarbamoyl)-ethyl]-carbamic acid benzyl ester (918309-76-9)

Conditions	Yield
With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide at 20℃; for 25h;	73%

O-benzylhydoxylamine hydrochloride (2687-43-6) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → ((S)-1-Benzyloxy-2,5-dioxo-pyrrolidin-3-yl)-carbamic acid benzyl ester

Conditions	Yield
In toluene for 1h; Heating;	72%

N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → N-benzyloxycarbonyl-L-aspartic acid α-p-nitrobenzyl ester (4668-44-4)

Conditions	Yield
	69%

p-toluidine (106-49-0) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → (S)-3-Benzyloxycarbonylamino-N-p-tolyl-succinamic acid + (S)-2-Benzyloxycarbonylamino-N-p-tolyl-succinamic acid

Conditions	Yield
With acetic acid In benzene for 0.166667h; Heating; Yields of byproduct given;	A 67% B n/a
In dimethyl sulfoxide for 0.333333h; Ambient temperature; Yield given. Yields of byproduct given;

4-methoxy-aniline (104-94-9) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → [(S)-1,2-Bis-(4-methoxy-phenylcarbamoyl)-ethyl]-carbamic acid benzyl ester

Conditions	Yield
Stage #1: N-benzyloxycarbonyl-L-aspartic acid anhydride In N,N-dimethyl-formamide at 20℃; for 3h; Stage #2: 4-methoxy-aniline With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide at 20℃; for 24h;	60%

methanol (67-56-1) + (3-methoxyphenyl)magnesium bromide (36282-40-3) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → (3S)-methyl 3-(benzyloxycarbonylamino)-4-(3-methoxyphenyl)-4-oxobutanoate + dimethyl (2S)-2-[(phenylmethoxy)carbonylamino]-butane-1,4-dioate (35909-93-4)

Conditions	Yield
Stage #1: (3-methoxyphenyl)magnesium bromide; N-benzyloxycarbonyl-L-aspartic acid anhydride In tetrahydrofuran at -78℃; for 4h; Stage #2: With citric acid In tetrahydrofuran at -78 - 20℃; Stage #3: methanol With thionyl chloride	A 60% B n/a

N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → (3S)-3-benzyloxycarbonylamino-4-hydroxybutanoic acid (94664-82-1)

Conditions	Yield
With sodium tetrahydroborate In tetrahydrofuran for 1h; Ambient temperature;	59%
Multi-step reaction with 2 steps 1: NaBH4 / tetrahydrofuran / 16 h / 20 °C 2: aq. CsCO3 / acetone / 3 h / 20 °C View Scheme

aniline (62-53-3) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → N-Benzyloxycarbonyl-L-asparaginsaeure-β-anilid (30750-71-1) + Cbz-Asp-anilide

Conditions	Yield
With acetic acid In benzene for 0.166667h; Heating; Yields of byproduct given;	A n/a B 58%
In dimethyl sulfoxide for 0.333333h; Ambient temperature; Yield given. Yields of byproduct given;

4-aminomethyl-benzoic acid ; hydrochloride (67688-72-6) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → (S)-4-((3-(benzyloxycarbonylamino)-2,5-dioxopyrrolidin-1-yl)methyl)benzoic acid (953435-25-1)

Conditions	Yield
Stage #1: 4-aminomethyl-benzoic acid ; hydrochloride; N-benzyloxycarbonyl-L-aspartic acid anhydride With pyridine; triethylamine at 20℃; for 9h; Stage #2: With acetic acid at 83℃; for 24h;	56%

methanol (67-56-1) + phenylmagnesium chloride (100-59-4) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → dimethyl (2S)-2-[(phenylmethoxy)carbonylamino]-butane-1,4-dioate (35909-93-4) + (3S)-methyl 3-(benzyloxycarbonylamino)-4-oxo-4-phenylbutanoate

Conditions	Yield
Stage #1: phenylmagnesium chloride; N-benzyloxycarbonyl-L-aspartic acid anhydride In tetrahydrofuran at -78℃; for 4h; Stage #2: With citric acid In tetrahydrofuran at -78 - 20℃; Stage #3: methanol With thionyl chloride	A n/a B 54%

methanol (67-56-1) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → (S)-2-benzyloxycarbonylamino-succinic acid 1-methyl ester (4668-42-2)

Conditions	Yield
Stage #1: methanol; N-benzyloxycarbonyl-L-aspartic acid anhydride In ethyl acetate at 20℃; for 5h; Stage #2: With N-cyclohexyl-cyclohexanamine In di-isopropyl ether Stage #3: With hydrogenchloride In water; ethyl acetate pH=2;	54%

N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → N-benzyloxycarbonyl-L-aspartic acid thioanhydride (1000278-32-9)

Conditions	Yield
With sodium sulfide; tetrabutylammomium bromide In dichloromethane; water for 3h;	47%
With sodium sulfide; tetrabutylammomium bromide In dichloromethane; water for 3h;	47%

1-(2-aminoethyl)-3-(benzyloxy)-2-methylpyridin-4(1H)-one hydrochloride salt + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → (S)-4-((2-(3-(benzyloxy)-2-methyl-4-oxopyridin-1(4H)-yl)ethyl)amino)-2-(((benzyloxy)carbonyl)amino)-4-oxobutanoic acid

Conditions	Yield
Stage #1: 1-(2-aminoethyl)-3-(benzyloxy)-2-methylpyridin-4(1H)-one hydrochloride salt With potassium hydroxide In methanol for 1h; Inert atmosphere; Stage #2: N-benzyloxycarbonyl-L-aspartic acid anhydride In N,N-dimethyl-formamide at 59.84℃; for 3h; Inert atmosphere;	44%

methanol (67-56-1) + n-butyl magnesium bromide (693-03-8) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → (S)-3-Benzyloxycarbonylamino-4-oxo-octanoic acid methyl ester + dimethyl (2S)-2-[(phenylmethoxy)carbonylamino]-butane-1,4-dioate (35909-93-4)

Conditions	Yield
Stage #1: n-butyl magnesium bromide; N-benzyloxycarbonyl-L-aspartic acid anhydride In tetrahydrofuran at -78℃; for 4h; Stage #2: With citric acid In tetrahydrofuran at -78 - 20℃; Stage #3: methanol With thionyl chloride	A 41% B n/a

N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) + 1-(3-aminopropyl)-3-(benzyloxy)-2-methylpyridin-4(1H)-one hydrochloride salt → (S)-4-((3-(3-(benzyloxy)-2-methyl-4-oxopyridin-1(4H)-yl)propyl)amino)-2-(((benzyloxy)carbonyl)amino)-4-oxobutanoic acid

Conditions	Yield
Stage #1: 1-(3-aminopropyl)-3-(benzyloxy)-2-methylpyridin-4(1H)-one hydrochloride salt With potassium hydroxide In methanol for 1h; Inert atmosphere; Stage #2: N-benzyloxycarbonyl-L-aspartic acid anhydride In N,N-dimethyl-formamide at 59.84℃; for 3h; Inert atmosphere;	22%

(S)-serine methyl ester (2788-84-3) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → N-(N-benzyloxycarbonyl-L-α-aspartyl)-L-serine methyl ester

Conditions	Yield
With chloroform

L-Valine methyl ester (4070-48-8) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → N-(N-benzyloxycarbonyl-L-α-aspartyl)-L-valine methyl ester (159879-61-5)

Conditions	Yield
With ethyl acetate
With potassium hydrogencarbonate; ethyl acetate

L-Valine methyl ester (4070-48-8) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → N-(N-benzyloxycarbonyl-L-α-aspartyl)-L-valine methyl ester (159879-61-5) + N-(N-benzyloxycarbonyl-L-β-aspartyl)-L-valine methyl ester (159879-62-6)

Conditions	Yield
With potassium hydrogencarbonate; ethyl acetate
With ethyl acetate

L-glutamic acid diethyl ester (16450-41-2) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → N-(N-benzyloxycarbonyl-L-β-aspartyl)-L-glutamic acid diethyl ester + N-(N-benzyloxycarbonyl-L-α-aspartyl)-L-glutamic acid diethyl ester (112842-55-4)

Conditions	Yield
With ethyl acetate

4-methyl pentanamine (5344-20-7) + N-benzyloxycarbonyl-L-aspartic acid anhydride (4515-23-5) → L-aspartic acid isohexyl imide (121790-47-4)

Conditions	Yield
at 130℃; Hydrieren des Reaktionsprodukts an Palladium/Kohle in Essigsaeure enthaltendem Aethanol;

Upstream product

• 1152-61-0 N-Cbz-L-Asp 
• 100-51-6 benzyl alcohol 
• 501-53-1 benzyl chloroformate 

Downstream Products

• 4515-20-2 Z-Asp-OBn 
• 39552-95-9 N-(N-benzyloxycarbonyl-L-α-aspartyl)-glycine ethyl ester 
• 6366-86-5 α-L-Asp-ε-L-Lys 
• 1152-61-0 N-Cbz-L-Asp 
• 87219-31-6 (3S)-3-benzyloxycarbonylamino-2-methyl-γ-butirolactone 
• 94718-14-6 (3S)-3-benzyloxycarbonylamino-2-ethyl-γ-butirolactone 
• 112308-34-6 (S)-3-Benzyloxycarbonylamino-2-ethyl-4-hydroxy-butyric acid 
• 94718-16-8 (2S,3S)-3-benzyloxycarbonylamino-2-isopropyl-γ-butirolactone 
• 94718-15-7 (3S)-3-benzyloxycarbonylamino-2-diethyl-γ-butirolactone 
• 94718-17-9 (2R,3S)-3-benzyloxycarbonylamino-2-<(1-hydroxy-1-methyl)-ethyl>-γ-butirolactone 
• 112308-42-6 (S)-3-Benzyloxycarbonylamino-4-hydroxy-2-(1-hydroxy-1-methyl-ethyl)-butyric acid 
• 112308-38-0 (3S)-2-ethyl-3-benzyloxycarbonylamino-4-(tert-butyldimethyl-silyloxy)butanoic acid 
• 112308-43-7 (2R,3S)-2-<(1-hydroxy-1-methyl)ethyl>-3-benzyloxycarbonyl-amino-4-tert-butyldimethylsilyloxybutanoic acid 
• 73618-80-1 N-(N-benzyloxycarbonyl-L-α-aspartyl)-L-glutamic acid 

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