42854-62-6

Basic information

• Product Name: L-Alanine benzyl ester 4-toluenesulfonate
• Synonyms: (S)-Benzyl 2-aminopropanoate 4-methylbenzenesulfonate;L-Alanine benzyl ester 4-toluenesulfonate salt≥ 99% (HPLC);L-Ala-OBzl·TosOH;ALANINE-OBZL P-TOSYLATE;L-ALANINE BENZYL ESTER 4-TOLUENESULFONATE;L-ALANINE BENZYL ESTER 4-TOLUENESULFONATE SALT;L-ALANINE BENZYL ESTER P-TOLUENESULFONATE;L-ALANINE BENZYL ESTER P-TOLUENESULFONATE SALT
• CAS NO: 42854-62-6
• Molecular Formula: C₇H₈O₃S*C₁₀H₁₃NO₂
• Molecular Weight: 351.42
• EINECS: 255-969-4
• Product Categories: Amino Acids Derivatives;Amino Acids;Alanine [Ala, A];Amino Acids and Derivatives;Amino Acids 13C, 2H, 15N;Amino Acid Benzyl Esters;Amino Acids (C-Protected);Biochemistry;Amino Acid Derivatives;Amino Acids & Derivatives;Aromatics;Chiral Reagents;Alanine;Peptide Synthesis
• Mol File: 42854-62-6.mol
• Article Data: 8

Chemical Properties

• Melting Point: 112-116 °C
• Boiling Point: 256.5 °C at 760 mmHg
• Flash Point: 119.6 °C
• Appearance: Yellowish oil
• Vapor Pressure: 0.0154mmHg at 25°C
• Refractive Index: -5.0 ° (C=3, MeOH)
• Storage Temp.: 0-6°C
• Solubility: DMSO, Methanol
• BRN: 3586474
• CAS DataBase Reference: L-Alanine benzyl ester 4-toluenesulfonate(CAS DataBase Reference)
• NIST Chemistry Reference: L-Alanine benzyl ester 4-toluenesulfonate(42854-62-6)
• EPA Substance Registry System: L-Alanine benzyl ester 4-toluenesulfonate(42854-62-6)

Safety Data

• Statements: 36/37/38
• Safety Statements: 22-24/25-44-35-28-26-7-4
• WGK Germany: 3
• Hazardous Substances Data: 42854-62-6(Hazardous Substances Data)

Usage

Chemical Properties

Yellowish Oil

InChI:InChI=1/C10H13NO2.C7H8O3S/c1-8(11)10(12)13-7-9-5-3-2-4-6-9;1-6-2-4-7(5-3-6)11(8,9)10/h2-6,8H,7,11H2,1H3;2-5H,1H3,(H,8,9,10)

Synthetic route

L-alanin (56-41-7) + toluene-4-sulfonic acid (104-15-4) + benzyl alcohol (100-51-6) → L-alanine benzyl ester p-toluenesulfonate (42854-62-6)

Conditions	Yield
In benzene for 10h; Reflux; Inert atmosphere;	100%
at 50 - 62℃; under 15.0015 Torr; for 5.5h;	98.6%
In cyclohexane; water for 4h; Dean-Stark; Reflux;	92%

toluene-4-sulfonic acid (104-15-4) + 4-polystyryltriphenylmethyl-Ala-OBzl → L-alanine benzyl ester p-toluenesulfonate (42854-62-6)

Conditions	Yield
In tetrahydrofuran at 35℃; for 2h;	88%

H-Ala-OBzl (17831-01-5) + toluene-4-sulfonic acid (104-15-4) → L-alanine benzyl ester p-toluenesulfonate (42854-62-6)

Conditions	Yield
In diethyl ether

BOC-glycine (4530-20-5) + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → Boc-Gly-Ala-OBzl (63649-08-1)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine	100%
With TEA; diphenyl phosphoryl azide In N,N-dimethyl-formamide 1.) 0 deg C, 4 h; 2.) r.t., overnight;	85%
Stage #1: BOC-glycine; L-alanine benzyl ester p-toluenesulfonate With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 0.166667h; Inert atmosphere; Stage #2: With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 24h; Inert atmosphere;

t-Boc-L-valine (13734-41-3) + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → Boc-Val-Ala-OBzl (77946-33-9)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine	100%

L-N-Boc-Ala (15761-38-3) + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → N-(tert-butoxycarbonyl)-L-alanyl-L-alanine benzyl ester (18670-98-9)

Conditions	Yield
With triethylamine; dicyclohexyl-carbodiimide In pyridine for 5h; Ambient temperature;	99%
With benzotriazol-1-ol; triethylamine; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide for 5h; Product distribution; Ambient temperature; other fluorinated alcohol and proton acceptor, other condensation reagents;	98%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine	96%

L-alanine benzyl ester p-toluenesulfonate (42854-62-6) + N-tert-butyloxycarbonyl di-L-tryptophan (90826-08-7) → Boc-Trp-Trp-Ala-OBzl (1311414-43-3)

Conditions	Yield
With 4-methyl-morpholine; benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 0℃; for 24h; pH=8;	98%
With 4-methyl-morpholine; benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 26h; pH=8;	98%

L-alanine benzyl ester p-toluenesulfonate (42854-62-6) + treprostinil (81846-19-7) → C33H45NO6

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane; water at 20℃; for 2.5h; Inert atmosphere;	97.8%

(S)-α-trifluoromethyl-proline + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → (S)-α-Tfm-Pro-L-Ala-OBn (1202059-56-0)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 48.3h;	95%

carbon dioxide (124-38-9) + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → (2S,2'S)-dibenzyl 2,2'-(carbonylbis(azanediyl))dipropanoate

Conditions	Yield
Stage #1: carbon dioxide; L-alanine benzyl ester p-toluenesulfonate With pyridine; 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at -20℃; for 0.5h; Stage #2: With thionyl chloride In dichloromethane at -20 - 20℃; for 2h; Inert atmosphere; Stage #3: L-alanine benzyl ester p-toluenesulfonate With pyridine at 20℃; for 4h; Inert atmosphere;	95%

Boc-N-Me-Val-OH (45170-31-8) + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → C21H32N2O5

Conditions	Yield
With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere;	94%

L-alanine benzyl ester p-toluenesulfonate (42854-62-6) + N-Trityl-L-Serin-Triethylammonium-Salz (111061-44-0) → Trt-L-Ser-L-Ala-OBn (790692-15-8)

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In chloroform at 23℃; for 12h;	92%
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In chloroform at 23℃; for 12h;	92%
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine In chloroform at 23℃; Inert atmosphere;	84%

(S)-3-hydroxy-2-(tritylamino)propanoic acid (4465-45-6) + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → Trt-L-Ser-L-Ala-OBn (790692-15-8)

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In chloroform at 23℃;	92%

L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → H-Ala-OBzl (17831-01-5)

Conditions	Yield
With triethylamine In water; toluene at 5℃; for 2.5h;	92%

N-picolinyl-α-aminoisobutyric acid (125686-76-2) + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → (S)-2-{2-Methyl-2-[(pyridine-2-carbonyl)-amino]-propionylamino}-propionic acid benzyl ester

Conditions	Yield
With benzotriazol-1-ol; triethylamine; dicyclohexyl-carbodiimide In tetrahydrofuran; acetonitrile for 72h; Ambient temperature;	90%

L-alanine benzyl ester p-toluenesulfonate (42854-62-6) + methyl 3,4,6-tri-O-acetyl-2-deoxy-2-(4-nitrophenoxycarbonylamino)-β-D-glucopyranoside (130539-23-0) → N-(methyl 3,4,6-tri-O-acetyl-2-amino-2-deoxy-β-D-glucopyranoside)-N'-carbamoyl-L-alanine benzyl ester

Conditions	Yield
With pyridine; triethylamine for 24h; Ambient temperature;	90%

L-alanine benzyl ester p-toluenesulfonate (42854-62-6) + monensin (17090-79-8) → 2-monensinamidopropanoic acid benzyl ester (122629-89-4)

Conditions	Yield
With 4-methyl-morpholine; benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 5℃; for 12h;	90%

L-alanine benzyl ester p-toluenesulfonate (42854-62-6) + O-phenyl phosphorodichloridate (770-12-7) → phenyl(benzyloxy-L-alaninyl)phosphorochloridate (183370-70-9)

Conditions	Yield
With triethylamine In dichloromethane at -78 - 20℃; for 2.5h;	90%
With triethylamine In dichloromethane at -78 - 20℃; for 4h; Inert atmosphere;	87%
With triethylamine In dichloromethane at -78 - 20℃; for 2.5h; Inert atmosphere;	87%
With triethylamine In dichloromethane at -78 - 20℃;

carbon dioxide (1111-72-4) + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) + (S)-tryptophan methyl ester hydrochloride (7524-52-9, 26988-71-6, 5619-09-0, 14907-27-8, 41222-70-2, 67557-19-1, 109492-62-8) → N-({(1S)-1-[(benzyloxy)carbonyl]ethyl}(13C)aminocarbonyl)-L-tryptophan methyl ester

Conditions	Yield
Stage #1: carbon dioxide; L-alanine benzyl ester p-toluenesulfonate With pyridine; 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at -20℃; for 0.5h; Stage #2: With thionyl chloride In dichloromethane at -20 - 20℃; for 2h; Inert atmosphere; Stage #3: (S)-tryptophan methyl ester hydrochloride With pyridine at 20℃; for 4h; Inert atmosphere;	90%

L-alanine benzyl ester p-toluenesulfonate (42854-62-6) + Fmoc-L-Gln(Trt)-OH (132327-80-1) → Fmoc-Gln(Trt)-Ala-OBzl ester (1381868-47-8)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In tetrahydrofuran at 20℃; for 3h; Inert atmosphere;	90%
Stage #1: L-alanine benzyl ester p-toluenesulfonate; Fmoc-L-Gln(Trt)-OH With triethylamine In dichloromethane for 0.0833333h; Stage #2: With benzotriazol-1-ol; dicyclohexyl-carbodiimide	79%

N-tert-butoxycarbonyl-L-allo-threonine (2592-18-9, 23082-29-3, 55674-67-4, 85979-33-5, 86748-77-8, 23082-30-6) + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → Boc-L-aThr-L-Ala-OBn (947189-54-0)

Conditions	Yield
With 1-hydroxy-7-aza-benzotriazole; sodium hydrogencarbonate; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane; N,N-dimethyl-formamide at -10 - 25℃; for 14h;	89%

1-naphthyl dichlorophosphate (31651-76-0) + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → 1-naphthyl(benzoxy-L-alaninyl)-phosphorochloridate (906670-24-4)

Conditions	Yield
With triethylamine In dichloromethane at -78 - 20℃;	89%
With triethylamine In dichloromethane at -78 - 20℃; for 3h; Inert atmosphere;	85%
With triethylamine In dichloromethane at -78 - 20℃; for 2.5h;	75%

C36H38N4O9 (1228178-29-7) + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → Fmoc-Asp(Bzl)-Ile-ψ(NH-CO-NH)-Ala-OBzl (1228178-51-5)

Conditions	Yield
With 4-methyl-morpholine In N,N-dimethyl-formamide at 20℃;	89%

C31H30N4O8 (1228178-31-1) + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → Fmoc-Ser(Bzl)-Gly-ψ(NH-CO-NH)-Ala-OBzl (1228178-53-7)

Conditions	Yield
With 4-methyl-morpholine In N,N-dimethyl-formamide at 20℃;	89%

C35H38N4O8 (1228178-33-3) + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → Fmoc-Ser(tBu)-Phe-ψ(NH-CO-NH)-Ala-OBzl (1228178-49-1)

Conditions	Yield
With 4-methyl-morpholine In N,N-dimethyl-formamide at 20℃;	89%

Z-Lys(Boc)-OH (2389-60-8) + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → Z-Lys(Boc)-Ala-OBn

Conditions	Yield
Stage #1: Z-Lys(Boc)-OH With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane for 0.5h; Inert atmosphere; Stage #2: L-alanine benzyl ester p-toluenesulfonate In dichloromethane at 22℃; for 4h; Inert atmosphere;	89%

Boc-Thr-OH (2592-18-9) + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → Boc-L-Thr-L-Ala-OBn (18671-01-7)

Conditions	Yield
With diphenylphosphoranyl azide; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 24h;	88%

bis(trichloromethyl) carbonate (32315-10-9) + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) + L-tryptophan tert-butyl ester hydrochloride → N-[[(1S)-1-[(benzyloxy)carbonyl]ethyl]carbamoyl]-L-tryptophan tert-butylester (286939-23-9)

Conditions	Yield
Stage #1: bis(trichloromethyl) carbonate; L-alanine benzyl ester p-toluenesulfonate With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.0833333h; Stage #2: L-tryptophan tert-butyl ester hydrochloride With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h; Further stages.;	88%

Boc-Glu(OBzl)-OH (13574-13-5) + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → tert-Butoxycarbonyl-L-glutamyl(ω-benzylester)-L-alanin-benzylester (53935-21-0)

Conditions	Yield
With hexachloroethane; benzotriazol-1-ol; Hexamethylphosphorous triamide In N,N-dimethyl-formamide	87%
With benzotriazol-1-ol; triethylamine In N,N-dimethyl-formamide at 20℃; for 24h; Condensation;	83%

(R)-α-trifluoromethyl-proline + L-alanine benzyl ester p-toluenesulfonate (42854-62-6) → (R)-α-Tfm-Pro-L-Ala-OBn (1202059-70-8)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 24.3h;	87%

L-alanine benzyl ester p-toluenesulfonate (42854-62-6) + 1',3'-dohexadecyl N--L-glutamate (171195-66-7) → 1',3'-dihexadecyl N-<1-(N-alanyl-O-benzyl ester)succinyl>-L-glutamate

Conditions	Yield
With triethylamine In ethyl acetate for 24h; Ambient temperature;	85%

Upstream product

• 17831-01-5 H-Ala-OBzl 
• 104-15-4 toluene-4-sulfonic acid 
• 56-41-7 L-alanin 
• 100-51-6 benzyl alcohol 

Downstream Products

• 4066-24-4 Z-Gly-Ala-OBzl 
• 18670-98-9 N-(tert-butoxycarbonyl)-L-alanyl-L-alanine benzyl ester 
• 53935-21-0 tert-Butoxycarbonyl-L-glutamyl(ω-benzylester)-L-alanin-benzylester 
• 82748-54-7 Ala-Ala-O-benzyl 
• 47094-07-5 (S)-2-((S)-2-Amino-3-methyl-butyrylamino)-propionic acid benzyl ester 
• 75779-22-5 H-Leu-Ala-OH 
• 73393-25-6 H-Phe-Ala-OBn 
• 188690-03-1 Boc-Gln-Ala-OBzl 
• 286939-23-9 N-[[(1S)-1-[(benzyloxy)carbonyl]ethyl]carbamoyl]-L-tryptophan tert-butylester 
• 413614-56-9 benzyl N-(1-prop-2-enyl)-L-alaninate 
• 1160859-66-4 Boc-Val-D-Pro-Gly-Ala-OBn 
• 1185198-28-0 N-[2-chloro-9-(tetrahydropyran-2-yl)-9H-purin-6-yl]-N-cyclopropylglycyl-L-alanine benzyl ester 
• 1333503-80-2 (2S)-benzyl 2-(((3R,5R)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yloxy)(phenoxy)phosphorylamino)propanoate 
• 1365030-58-5 O-benzyl N-(6-chloro-2,5-dioxo-4-methoxy-1,4-cyclohexadienyl)-L-alanine 

Relevant articles and documents

One-step preparation of enantiopure l- or d-amino acid benzyl esters avoiding the use of banned solvents

The enantiomers of amino acid benzyl esters are very important synthetic intermediates. Many of them are currently prepared by treatment with benzyl alcohol and p-toluenesulfonic acid in refluxing benzene or carbon tetrachloride, to azeotropically remove water, and then precipitated as tosylate salt by adding diethyl ether. Here, we report a very efficient preparation of eight l- or d-amino acid benzyl esters (Ala, Phe, Tyr, Phg, Val, Leu, Lys, Ser), in which these highly hazardous solvents are dismissed using cyclohexane as a water azeotroping solvent and ethyl acetate to precipitate the tosylate salt. With some work-up modifications and lower yield, the procedure can be applied also to methionine. Chiral HPLC analysis shows that all the benzyl esters, including the highly racemizable ones such as those of phenylglycine, tyrosine and methionine, are formed enantiomerically pure under these new reaction conditions thus validating the solvents replacement. Contrariwise, toluene cannot be used in place of benzene or carbon tetrachloride because leading to partially or totally racemized amino acid benzyl esters depending on the polar effect of the amino acid α-side chain as expressed by Taft’s substituent constant (σ*).

Asymmetric α-2-tosylethenylation of N,N-dialkyl-l-amino acid esters via the formation of non-racemic ammonium enolates

Asymmetric α-2-tosylethenylation of (S)-2-(pyrrolidin-1-yl)propanoic acid esters was shown to produce good yields with high enantioselectivities. The reaction proceeds via the formation of a non-racemic ammonium enolate without an external source of chirality.

PROCESS FOR PRODUCTION OF OPTICALLY ACTIVE ALPHA-AMINO ACID BENZYL ESTER

A method of producing optically active α-amino acid benzyl esters comprising reacting an optically active α-amino acid and benzyl alcohols in the presence of an acid, wherein the reaction is carried out under reduced pressure without substantially using a solvent, while distilling off water generated by the progress of the reaction.