73821-97-3

Basic information

• Product Name: Boc-L-glutamic acid 5-cyclohexyl ester
• Synonyms: N-ALPHA-TERT-BUTYLOXYCARBONYL-L-GLUTAMIC ACID GAMMA-CYCLOHEXYL ESTER;N-BOC-L-GLUTAMIC ACID 5-CYCLOHEXYL ESTER;N-(TERT-BUTOXYCARBONYL)-L-GLUTAMIC ACID 5-CYCLOHEXYL ESTER;N-T-BUTOXYCARBONYL-L-GLUTAMIC ACID 5-CYCLOHEXYL ESTER;T-BUTYLOXYCARBONYL-L-GLUTAMIC ACID GAMMA-CYCLOHEXYL ESTER;N-T-boc-L-glutamic acid gamma-*cyclohexyl ester F;N-tert-Butoxycarbonyl-L-glutamic acid cyclohexyl ester;Boc-L-Glutamic Acid Cyclohexyl Ester
• CAS NO: 73821-97-3
• Molecular Formula: C₁₆H₂₇NO₆
• Molecular Weight: 329.39
• Product Categories: Amino Acid Derivatives;Amino Acids;Glutamic acid [Glu, E];Boc-Amino Acids and Derivative
• Mol File: 73821-97-3.mol
• Article Data: 2

Chemical Properties

• Melting Point: 54-57 °C
• Boiling Point: 502.6 °C at 760 mmHg
• Flash Point: 257.8 °C
• Appearance: /Solid
• Density: 1.16 g/cm³
• Vapor Pressure: 1.82E-11mmHg at 25°C
• Refractive Index: 1.497
• Storage Temp.: 2-8°C
• PKA: 3.79±0.10(Predicted)
• CAS DataBase Reference: Boc-L-glutamic acid 5-cyclohexyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: Boc-L-glutamic acid 5-cyclohexyl ester(73821-97-3)
• EPA Substance Registry System: Boc-L-glutamic acid 5-cyclohexyl ester(73821-97-3)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 73821-97-3(Hazardous Substances Data)

Usage

Chemical Properties

White to off-white powder

Uses

This side-chain protecting group for glutamic acid, Boc-L-glutamic acid 5-cyclohexyl ester is used to minimize side reactions during acidic and basic treatments

InChI:InChI=1/C16H27NO6/c1-16(2,3)23-15(21)17-12(14(19)20)9-10-13(18)22-11-7-5-4-6-8-11/h11-12H,4-10H2,1-3H3,(H,17,21)(H,19,20)/t12-/m0/s1

Synthetic route

N-Boc-Glu(OcHex)-PAM resin → N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester

Conditions	Yield
With trimethyltin(IV) hydroxide In 1,2-dichloro-ethane for 10h; Heating;	100%

N-Boc-Glu(OcHex)-Merrifield resin → N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3)

Conditions	Yield
With trimethyltin(IV) hydroxide In 1,2-dichloro-ethane for 12h; Heating;	97%

di-tert-butyl dicarbonate (24424-99-5) + γ-cyclohexyl L-glutamate (112471-82-6) → N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3)

Conditions	Yield
With N,N,N',N'-tetramethylguanidine In N,N-dimethyl-formamide for 12h; Ambient temperature; Yield given;

L-glutamic acid (56-86-0) → N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2SO4 / diethyl ether / 2 h / 70 °C 2: 1,1,3,3-tetramethylguanidine / dimethylformamide / 12 h / Ambient temperature View Scheme

cyclohexanol (108-93-0) + nitrogen → N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2SO4 / diethyl ether / 2 h / 70 °C 2: 1,1,3,3-tetramethylguanidine / dimethylformamide / 12 h / Ambient temperature View Scheme

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) → L-glutamic acid (56-86-0)

Conditions	Yield
With phenylthiotrimethylsilane; pertrimethylsilylated Nafion; 3-methyl-phenol; trifluoroacetic acid for 3h;	100%

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + (S)-2-azido-3-hydroxypropionic acid methyl ester (162463-99-2) → methyl (2S,2'S)-2-azido-3-(N-Boc-ω-cyclohexyl-glutamyloxy)propionate (940950-90-3)

Conditions	Yield
With dmap; diisopropyl-carbodiimide In dichloromethane at 0 - 20℃;	99%
Stage #1: N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0℃; for 0.25h; Inert atmosphere; Stage #2: (S)-2-azido-3-hydroxypropionic acid methyl ester In dichloromethane at 0 - 20℃; Inert atmosphere;	99%

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + (S)-2-[(S)-2-((S)-2-{(S)-2-[(S)-2-((S)-2-Amino-4-carbamoyl-butyrylamino)-4-cyclohexyloxycarbonyl-butyrylamino]-6-benzyloxycarbonylamino-hexanoylamino}-4-carbamoyl-butyrylamino)-propionylamino]-6-benzyloxycarbonylamino-hexanoic acid benzyl ester → Boc-Glu(OcHex)-Gln-Glu(OcHex)-Lys(Z)-Gln-Ala-Lys(Z)-OBzl (114855-99-1)

Conditions	Yield
With 4-methyl-morpholine; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide at 4℃; for 8h;	96%

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + H-Tfeg-Tfeg-Lys(ClZ)-OTce*HCl → Boc-Glu(OcHex)-Tfeg-Tfeg-Lys(ClZ)-OTce (266325-39-7)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; Acylation;	96%

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + TFA*Ser-OBn → Boc-Glu(OcHx)-Ser-OBzl

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 6h;	96%

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + H-Ala-Glu(O-Chx)-Lys(2-Adoc)-Cys(MeBzl)-OBzl*TFA → Boc-Glu(O-Chx)-Ala-Glu(O-Chx)-Lys(2-Adoc)-Cys(MeBzl)-OBzl

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine In dichloromethane for 2h; Ambient temperature;	95.1%

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) → Boc-Glu(OcHx)-NH2 (138848-57-4)

Conditions	Yield
Stage #1: N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.333333h; Stage #2: With ammonium hydroxide In dichloromethane for 1.5h; Further stages.;	95%

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) → Boc-Glu (2419-94-5)

Conditions	Yield
With magnesium; hydrazinium monoformate In methanol at 25℃; for 2h;	94%

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + (S)-2-{(S)-2-[(S)-2-((S)-2-Amino-6-benzyloxycarbonylamino-hexanoylamino)-4-carbamoyl-butyrylamino]-propionylamino}-6-benzyloxycarbonylamino-hexanoic acid benzyl ester → Boc-Glu(OcHex)-Lys(Z)-Gln-Ala-Lys(Z)-OBzl (114856-05-2)

Conditions	Yield
With 4-methyl-morpholine; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide at 4℃; for 8h;	91%

BOC-glycine (4530-20-5) + N-tert-butoxycarbonyl-L-leucine (13139-15-6) + N-Boc-Lys(ClZ)-OH (33640-54-9) + N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + Boc-Ala-His(Bom)-Ala-(p-nitrobenzophenone oxime resin)C6H5CH2OC(O)X → Boc-Ala-His(Bom)-Ala-Glu(OcHex)-Leu-Leu-Lys(ClZ)-Gly-OBzl

Conditions	Yield
Multistep reaction;	91%

N-tert-butoxycarbonyl-L-leucine (13139-15-6) + L-N-Boc-Ala (15761-38-3) + N-Boc-Lys(ClZ)-OH (33640-54-9) + N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3)

Conditions	Yield
Multistep reaction;	91%

N-tert-butoxycarbonyl-L-leucine + L-N-Boc-Ala (15761-38-3) + N-Boc-Lys(ClZ)-OH (33640-54-9) + N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + Boc-D-Ala-Pro-(p-nitrobenzophenone oxime resin) → Boc-D-Ala-Pro-Ala-Glu(OcHex)-Leu-Leu-Lys(ClZ)-OH

Conditions	Yield
Multistep reaction;	91%

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + α-bromoacetophenone (70-11-1) → Boc-Glu(OcHex)-OPac (123167-66-8)

Conditions	Yield
With triethylamine In ethyl acetate	89%
With caesium carbonate 1.) EtOH, H2O, 2.) DMF, RT; Yield given. Multistep reaction;

t-Boc-L-valine (13734-41-3) + L-N-Boc-Ala (15761-38-3) + N-Boc-Lys(ClZ)-OH (33640-54-9) + N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + Boc-Ala-D-Ala-Pro-(p-nitrobenzophenone oxime resin) → Boc-Ala-D-Ala-Pro-Ala-Val-Glu(OcHex)-Val-Lys(ClZ)-Val-Ala-OH

Conditions	Yield
Multistep reaction;	88%

t-Boc-L-valine (13734-41-3) + L-N-Boc-Ala (15761-38-3) + N-Boc-Lys(ClZ)-OH (33640-54-9) + N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + Z-Ala-D-Ala-Pro-Ala--(p-nitrobenzophenone oxime resin) → Z-Ala-D-Ala-Pro-Ala-Orn[4-(10,15,20-tritolylporphyrin-5-yl)benzoyl]-Glu(OcHex)-Val-Lys(ClZ)-Val-Ala-OH

Conditions	Yield
Multistep reaction;	88%

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + isopropylamine (75-31-0) → Boc-L-Glu(OcHx)-NH-i-Pr

Conditions	Yield
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine In chloroform	88%

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + H-Lys(2-Adoc)-Gln-Lys(2-Adoc)-OBzl*HCl → Boc-Glu(O-cHex)-Lys(2-Adoc)-Gln-Lys(2-Adoc)-OBzl (249302-38-3)

Conditions	Yield
With benzotriazol-1-ol; triethylamine; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 4℃; Acylation;	84.5%

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + H-Lys(2-Adoc)-Cys(MeBzl)-OBzl*TFA → Boc-Glu(O-Chx)-Lys(2-Adoc)-Cys(MeBzl)-OBzl

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine In dichloromethane for 2h; Ambient temperature;	79.8%

N-(fluoren-9-ylmethoxycarbonyl)glycine (29022-11-5) + Fmoc-Lys(Z)-OH (86060-82-4) + N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) → Boc-Glu(OcHx)GlyLys(Z)-OH

Conditions	Yield
Multistep reaction;	79%

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + N'-((S)-2-{(S)-2-[(S)-2-((S)-2-Amino-3-methyl-butyrylamino)-3-carbamoyl-propionylamino]-3-benzyloxy-propionylamino}-3-phenyl-propionyl)-hydrazinecarboxylic acid 2,2,2-trichloro-ethyl ester → Boc-Glu(OcHex)-Ile-Asn-Ser(Bzl)-Phe-NHNH-Troc

Conditions	Yield
With 4-methyl-morpholine; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide at 4℃; for 8h;	78%

L-Ala-OPAc (53100-33-7) + N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) → Boc-Glu(OcHex)-Ala-OPac (141795-10-0)

Conditions	Yield
With benzotriazol-1-ol; triethylamine; dicyclohexyl-carbodiimide In tetrahydrofuran	77%

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + H-Glu(O-Chx)-Gly-OBzl*TFA → Boc-Glu(O-Chx)-Glu(O-Chx)-Gly-OBzl

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine In dichloromethane for 3h; Ambient temperature;	72.9%

BOC-glycine (4530-20-5) + Boc-(R)-Ala (3744-87-4, 7764-95-6, 15761-38-3) + N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) + N-Boc-O-benzyl-L-threonine (15260-10-3) + Boc-Arg(Tos)-OH (13836-37-8) + BOC-O-benzyl-L-serine (23680-31-1) + Boc-Asp(O-cyclohexyl)-OH (73821-95-1) + N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + Boc-(S)-Lys(2-Cl-Z)-OH (54613-99-9) + (S)-3-[4-(2-Bromo-benzyloxycarbonyloxy)-phenyl]-2-tert-butoxycarbonylamino-propionic acid (47689-67-8) + N(α)-t-butoxycarbonyl-N(ϖ)-benzyloxymethyl-L-histidine (83468-83-1) → H-HAEGTFTSDVSSYLEGQA-[D-Ala]-CKEFIAWLVKGR-NH2

Conditions

Yield

Stage #1: Boc-Arg(Tos)-OH With 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V); N-ethyl-N,N-diisopropylamine; 6-chloro-1-hydroxybenzotriazole In 1-methyl-pyrrolidin-2-one for 0.5h; solid phase reaction; Stage #2: With trifluoroacetic acid In 1-methyl-pyrrolidin-2-one solid phase reaction; Stage #3: BOC-glycine; Boc-(R)-Ala; N-tert-butoxycarbonyl-L-phenylalanine; N-Boc-O-benzyl-L-threonine; BOC-O-benzyl-L-serine; Boc-Asp(O-cyclohexyl)-OH; N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester; Boc-(S)-Lys(2-Cl-Z)-OH; (S)-3-[4-(2-Bromo-benzyloxycarbonyloxy)-phenyl]-2-tert-butoxycarbonylamino-propionic acid; N(α)-t-butoxycarbonyl-N(ϖ)-benzyloxymethyl-L-histidine Further stages;

71%

...Expand

Gly-OBz (1738-68-7) + N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) → (S)-4-(Benzyloxycarbonylmethyl-carbamoyl)-4-tert-butoxycarbonylamino-butyric acid cyclohexyl ester (142828-14-6)

Conditions	Yield
With benzotriazol-1-ol; triethylamine; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 4℃;	70%
With 4-methyl-morpholine; isobutyl chloroformate

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + benzyl bromide (100-39-0) → (2S)-tert-butoxycarbonylamino-pentanedioic acid 1-benzyl ester 5-cyclohexyl ester (73821-96-2)

Conditions	Yield
With caesium carbonate In methanol	70%
With triethylamine In N,N-dimethyl-formamide at 25℃; for 5h;	67%

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + glycine benzyl ester p-toluenesulfonic acid salt (1738-76-7) → (S)-4-(Benzyloxycarbonylmethyl-carbamoyl)-4-tert-butoxycarbonylamino-butyric acid cyclohexyl ester (142828-14-6)

Conditions	Yield
With benzotriazol-1-ol; triethylamine; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 4℃;	66.9%

N-α-tert-butyloxycarbonyl-glutamic acid, γ-cyclohexyl ester (73821-97-3) + H-Lys(2-Adoc)-Asp(O-2-Ada)-Ala-Pro-OBzl*HCl → Boc-Glu(O-cHex)-Lys(2-Adoc)-Asp(O-2-Ada)-Ala-Pro-OBzl (249302-47-4)

Conditions	Yield
With benzotriazol-1-ol; triethylamine; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 4℃; Acylation;	64.7%

Upstream product

• 108-93-0 cyclohexanol 
• 56-86-0 L-glutamic acid 
• 24424-99-5 di-tert-butyl dicarbonate 
• 112471-82-6 γ-cyclohexyl L-glutamate 

Downstream Products

• 266325-39-7 Boc-Glu(OcHex)-Tfeg-Tfeg-Lys(ClZ)-OTce 
• 137339-65-2 Ser-Phe-Leu-Leu-Arg-Asn-Pro-Asn-Asp-Lys-Tyr-Glu-Pro-Phe-OH 
• 398476-84-1 4-tert-butoxycarbonylamino-4-(2'-tert-butylsulfamoyl-biphenyl-4-ylcarbamoyl)-butyric acid cyclohexyl ester 

Relevant articles and documents

Selective detachment of Boc-protected amino acids and peptides from Merrifield, PAM and Wang resins by trimethyltin hydroxide

We describe the development of a new non-acidolytic and non- nucleophilic method for the selective cleavage by trimethyltin hydroxide of amino acids and dipeptides at benzyl ester links attached to resins commonly used in peptide synthesis.