34079-31-7

Basic information

• Product Name: Z-PRO-NH2
• Synonyms: N-ALPHA-CARBOBENZOXY-L-PYRROLIDINE-2-CARBOXYLIC ACID ALPHA-AMIDE;N-ALPHA-CARBOBENZOXY-L-PROLINE AMIDE;N-CARBOBENZOXY-L-PROLINE AMIDE;(S)-2-CARBAMOYL-1-CBZ-PYRROLIDINE;(S)-2-CARBAMOYL-PYRROLIDINE-1-CARBOXYLIC ACID BENZYL ESTER;(S)-1-N-CBZ-PROLINAMIDE;Z-L-PROLINAMIDE;Z-L-PROLINE AMIDE
• CAS NO: 34079-31-7
• Molecular Formula: C₁₃H₁₆N₂O₃
• Molecular Weight: 248.28
• EINECS: 231-397-0
• Product Categories: Proline [Pro, P];Z-Amino Acids and Derivatives;Z-Amino acid series
• Mol File: 34079-31-7.mol
• Article Data: 35

Chemical Properties

• Melting Point: 90-95℃
• Boiling Point: 465.6 °C at 760 mmHg
• Flash Point: 235.4 °C
• Appearance: /Solid
• Density: 1.263 g/cm³
• Vapor Pressure: 7.61E-09mmHg at 25°C
• Refractive Index: 1.581
• Storage Temp.: Store at RT.
• Solubility: soluble in Methanol
• PKA: 15.95±0.20(Predicted)
• CAS DataBase Reference: Z-PRO-NH2(CAS DataBase Reference)
• NIST Chemistry Reference: Z-PRO-NH2(34079-31-7)
• EPA Substance Registry System: Z-PRO-NH2(34079-31-7)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38
• Safety Statements: 36
• WGK Germany: 3
• Hazardous Substances Data: 34079-31-7(Hazardous Substances Data)

Usage

Chemical Properties

White crystals

InChI:InChI=1/C13H16N2O3/c14-12(16)11-7-4-8-15(11)13(17)18-9-10-5-2-1-3-6-10/h1-3,5-6,11H,4,7-9H2,(H2,14,16)/t11-/m0/s1

Synthetic route

N-Benzyloxycarbonyl-L-proline (1148-11-4) → Z-Pro-NH2 (34079-31-7)

Conditions	Yield
With ammonium hydroxide; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 20℃; for 24h;	100%
With ammonium hydroxide; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride at 20℃;	100%
Stage #1: N-Benzyloxycarbonyl-L-proline With 4-methyl-morpholine; chloroformic acid ethyl ester In tetrahydrofuran at 0℃; for 0.25h; Stage #2: With ammonia In tetrahydrofuran; water at 0 - 20℃; for 15h;	100%

N-benzyloxycarbonyl-L-proline p-nitrophenyl ester (3304-59-4) → Z-Pro-NH2 (34079-31-7)

Conditions	Yield
With ammonia; triethylamine In methanol at 0℃; Reflux;	90%

(S)-benzyloxycarbonyl-proline acid chloride (61350-60-5, 61350-62-7, 89705-40-8, 106709-50-6) → Z-Pro-NH2 (34079-31-7)

Conditions	Yield
With ammonia In dichloromethane at 0 - 20℃; Large scale;	82%
With ammonia In tetrahydrofuran at 0 - 20℃; for 1h;

benzyl chloroformate (501-53-1) + L-prolinamide (7531-52-4) → Z-Pro-NH2 (34079-31-7)

Conditions	Yield
With sodium hydrogencarbonate In tetrahydrofuran; water at 0 - 20℃;	76%
With sodium hydroxide

(2S)-2-[({(2S)-1-[(benzyloxy)carbonyl]tetrahydro-1H-pyrrol-2-yl}carbonyl)amino]propanoic acid (14030-00-3) → N2-(Benzyloxycarbonyl)-N1-(1'-hydroxyethyl)-L-prolinamid + Z-Pro-NH2 (34079-31-7)

Conditions	Yield
With acetic acid; N-ethyl-N,N-diisopropylamine anodic oxidation; Pt electrodes, i = 250 mA*cm-2, current equiv.: 13.4 F/mol;	A 50% B 12%

N2-(Benzyloxycarbonyl)-N1-(1'-hydroxyethyl)-L-prolinamid → Z-Pro-NH2 (34079-31-7)

Conditions	Yield
With trifluoroacetic acid In water at 30℃; for 6h; Yield given;

N-carbobenzoxyprolylglycine (2766-18-9) → Z-Pro-NH2 (34079-31-7)

Conditions	Yield
With methanol; N-ethyl-N,N-diisopropylamine; trifluoroacetic acid 1.) anodic oxidation; Pt electrodes, i = 250 mA*cm-2, current equiv.: 16.5 F/mol, 2.) H2O, 25 deg C, 8 h; Yield given. Multistep reaction;

(S)-2-Ethoxycarbonyloxycarbonyl-pyrrolidine-1-carboxylic acid benzyl ester → Z-Pro-NH2 (34079-31-7)

Conditions	Yield
With ammonia In dichloromethane at -20℃; for 1h; Yield given;
With ammonium hydroxide In tetrahydrofuran at 0℃; for 0.75h; Yield given;
With ammonia In water for 4h;

benzyl chloroformate (501-53-1) + D-lysine → Z-Pro-NH2 (34079-31-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 90 percent / aq. NaOH / 2 h / 5 °C 2: 96 percent / di-tert-butyl pyrocarbonate; ammonium hydrogencarbonate; pyridine / acetonitrile / 68 h View Scheme
Multi-step reaction with 2 steps 1.1: Boc2O 1.2: 96 percent / NH4HCO3 View Scheme

L-proline (147-85-3) → Z-Pro-NH2 (34079-31-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 90 percent / aq. NaOH / 2 h / 5 °C 2: 96 percent / di-tert-butyl pyrocarbonate; ammonium hydrogencarbonate; pyridine / acetonitrile / 68 h View Scheme
Multi-step reaction with 2 steps 1.1: Boc2O 1.2: 96 percent / NH4HCO3 View Scheme
Multi-step reaction with 2 steps 1: sodium hydroxide / H2O / Ambient temperature 2: 1.) triethylamine, isobutyl chloroformate, 2.) ammonia / 1.) chloroform, 0 deg C, 2 h, 2.) chloroform, RT, overnight View Scheme
Multi-step reaction with 2 steps 1: sodium hydroxide / 2 h / 5 °C 2: di-tert-butyl dicarbonate; ammonium bicarbonate; pyridine / acetonitrile / 68 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate / toluene / 2 h / 10 - 20 °C 2: thionyl chloride / toluene / 4 h / Reflux 3: ammonia / dichloromethane / 0 - 20 °C / Large scale View Scheme

(2S)-2-[({(2S)-1-[(benzyloxy)carbonyl]tetrahydro-1H-pyrrol-2-yl}carbonyl)amino]propanoic acid (14030-00-3) → Z-Pro-NH2 (34079-31-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 50 percent / AcOH, EtN(i-Pr)2 / anodic oxidation; Pt electrodes, i = 250 mA*cm-2, current equiv.: 13.4 F/mol 2: 70 percent CF3COOH / H2O / 6 h / 30 °C View Scheme

benzyl chloroformate (501-53-1) → Z-Pro-NH2 (34079-31-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / H2O / Ambient temperature 2: 1.) triethylamine, isobutyl chloroformate, 2.) ammonia / 1.) chloroform, 0 deg C, 2 h, 2.) chloroform, RT, overnight View Scheme
Multi-step reaction with 2 steps 1: sodium hydroxide / 2 h / 5 °C 2: di-tert-butyl dicarbonate; ammonium bicarbonate; pyridine / acetonitrile / 68 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate / toluene / 2 h / 10 - 20 °C 2: thionyl chloride / toluene / 4 h / Reflux 3: ammonia / dichloromethane / 0 - 20 °C / Large scale View Scheme

N-carbobenzoxy-L-proline phenylmethyl ester (124980-30-9) → Z-Pro-NH2 (34079-31-7)

Conditions	Yield
With ammonia In methanol at 20℃; for 120h; sealed bottle;

C16H19NO5 (60433-33-2) → Z-Pro-NH2 (34079-31-7)

Conditions	Yield
With ammonia In dichloromethane; water

Z-Pro-NH2 (34079-31-7) → (2S)-2-cyanopyrrolidine-1-carboxylic acid benzyl ester (63808-36-6)

Conditions	Yield
Stage #1: Z-Pro-NH2 With p-toluenesulfonyl chloride In pyridine at 100℃; for 3h; Stage #2: With hydrogenchloride In pyridine; water at 20℃;	100%
With 1,3,5-trichloro-2,4,6-triazine In N,N-dimethyl-formamide at 0 - 20℃; for 4h; Inert atmosphere;	99%
With 1,3,5-trichloro-2,4,6-triazine In N,N-dimethyl-formamide at 0 - 20℃; for 4h;	97%

Z-Pro-NH2 (34079-31-7) → L-prolinamide (7531-52-4)

Conditions	Yield
With 10% palladium on carbon; hydrogen In methanol for 7h;	100%
With hydrogen; palladium on activated charcoal In methanol for 9h; Ambient temperature;	88.4%
With hydrogen; palladium on activated charcoal In methanol under 2068.6 Torr; for 5h;	87%
With hydrogen; palladium In methanol for 3h;

N,N-dimethyl-formamide dimethyl acetal (4637-24-5) + Z-Pro-NH2 (34079-31-7) → benzyl (2S)-2-(dimethylaminomethylenecarbamoyl)pyrrolidine-1-carboxylate

Conditions	Yield
at 20 - 120℃; for 2h;	100%

Z-Pro-NH2 (34079-31-7) → Cbz-L-proline thioamide (63808-47-9)

Conditions	Yield
With Lawessons reagent In toluene at 20 - 100℃; for 3h;	100%
With Lawessons reagent In tetrahydrofuran at 65℃;	100%
With Lawessons reagent In dichloromethane at 20℃;	80%

ethyl (E)-3-bromoacrylate (31930-35-5) + Z-Pro-NH2 (34079-31-7) → benzyl (S,E)-2-(3-ethoxy-3-oxoprop-1-enylcarbamoyl)pyrrolidine-1-carboxylate (1005796-57-5)

Conditions	Yield
Stage #1: Z-Pro-NH2 With cetyltrimethylammonim bromide; potassium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; palladium diacetate In toluene at 50 - 55℃; for 1h; Stage #2: ethyl (E)-3-bromoacrylate In water; toluene Heating; Further stages.;	92%

benzoyl isocyanate (4461-33-0) + Z-Pro-NH2 (34079-31-7) → benzyl (S)-2-((benzoylcarbamoyl)carbamoyl)pyrrolidine-1-carboxylate (1419208-71-1)

Conditions	Yield
In toluene for 2h; Inert atmosphere; Reflux;	89%

di-tert-butyl dicarbonate (24424-99-5) + Z-Pro-NH2 (34079-31-7) → Z-Pro-N(Boc)2 (96308-19-9)

Conditions	Yield
With dmap In acetonitrile for 5h; Ambient temperature;	87%

methyl 3,3,3-trifluoropyruvate (13089-11-7) + Z-Pro-NH2 (34079-31-7) → (S)-2-(2,2,2-Trifluoro-1-hydroxy-1-methoxycarbonyl-ethylcarbamoyl)-pyrrolidine-1-carboxylic acid benzyl ester

Conditions	Yield
Ambient temperature;	83%

phenyl isocyanate (103-71-9) + Z-Pro-NH2 (34079-31-7) → C20H21N3O4 (1429472-14-9)

Conditions	Yield
In toluene for 40h; Inert atmosphere; Reflux;	82%

ethyl 2-diazo-2-(diethoxyphosphoryl)acetate (17507-56-1) + Z-Pro-NH2 (34079-31-7) → Ethyl 2-[(S)-2-(1-benzyloxycarbonylpyrrolidin-2-yl)carbonyl]amino-2-(diethoxyphosphoryl)acetate

Conditions	Yield
dirhodium tetraacetate In toluene Heating;	80%
dirhodium tetraacetate In toluene for 2h; Substitution; Heating;	80%

2-Diazo-3-oxo-butyric acid methyl ester (24762-04-7) + Z-Pro-NH2 (34079-31-7) → (S)-2-(1-Methoxycarbonyl-2-oxo-propylcarbamoyl)-pyrrolidine-1-carboxylic acid benzyl ester (182866-68-8)

Conditions	Yield
dirhodium tetraacetate In chloroform for 0.5h; Heating;	74%

Z-Pro-NH2 (34079-31-7) → 2-(S)-aminomethyl-pyrrolidine-1-carboxylic acid benzyl ester (119020-03-0, 141774-68-7)

Conditions	Yield
Stage #1: Z-Pro-NH2 With borane In tetrahydrofuran for 7h; Heating; Stage #2: With hydrogenchloride for 6h; Heating; Further stages.;	74%
Stage #1: Z-Pro-NH2 With borane In tetrahydrofuran at 0℃; for 7h; Heating / reflux; Stage #2: With hydrogenchloride; water In tetrahydrofuran at 0℃; for 6h; Heating / reflux; Stage #3: With sodium hydroxide In tetrahydrofuran; water pH=8;	74%

(S)-ethyl 5-phenyl-4-phenylselenylpent-2-(E)-enoate (1248344-51-5) + Z-Pro-NH2 (34079-31-7) → (S)-benzyl 2-((S)-1-ethoxycarbonyl-4-phenylbut-2-enylcarbamoyl)pyrrolidine-1-carboxylate

Conditions	Yield
Stage #1: (S)-ethyl 5-phenyl-4-phenylselenylpent-2-(E)-enoate; Z-Pro-NH2 With toluene-4-sulfonic acid; trimethyl orthoformate In methanol for 0.5h; Stage #2: With N-chloro-succinimide; N-ethyl-N,N-diisopropylamine In methanol at 0℃; for 0.333333h;	60%

2-Oxobutyric acid (600-18-0) + Z-Pro-NH2 (34079-31-7) → Nα-benzyloxycarbonyl-L-prolyl-(Z)-α,β-dehydrobutyrine

Conditions	Yield
With toluene-4-sulfonic acid In benzene for 5h; Heating;	40%

triphenyl phosphite (101-02-0) + isovaleraldehyde (590-86-3) + Z-Pro-NH2 (34079-31-7) → (S)-2-[1-(Diphenoxy-phosphoryl)-3-methyl-butylcarbamoyl]-pyrrolidine-1-carboxylic acid benzyl ester (82818-47-1)

Conditions	Yield
With copper(II) bis(trifluoromethanesulfonate) In dichloromethane at 20℃; for 48h; Reagent/catalyst;	38%

4-bromo-5-ethoxyfuran-2(5H)-one (32978-38-4) + Z-Pro-NH2 (34079-31-7) → benzyl (2S)-2-((2R)-2-ethoxy-5-oxo-2,5-dihydrofuran-3-ylcarbamoyl)pyrrolidine-1-carboxylate (865838-95-5) + benzyl (2S)-2-((2S)-2-ethoxy-5-oxo-2,5-dihydrofuran-3-ylcarbamoyl)pyrrolidine-1-carboxylate (865838-96-6)

Conditions	Yield
Stage #1: Z-Pro-NH2 With cetyltrimethylammonim bromide; potassium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; palladium diacetate In toluene at 50℃; for 1h; Stage #2: In water; toluene for 0.25h; Stage #3: 4-bromo-5-ethoxyfuran-2(5H)-one In water; toluene at 50℃; for 7h; Further stages.;	A 33% B n/a

triphenyl phosphite (101-02-0) + benzaldehyde (100-52-7) + Z-Pro-NH2 (34079-31-7) → C32H31N2O6P

Conditions	Yield
With copper(II) bis(trifluoromethanesulfonate) In dichloromethane at 20℃; for 48h; Reagent/catalyst;	31%

triphenyl phosphite (101-02-0) + acetaldehyde (75-07-0) + Z-Pro-NH2 (34079-31-7) → C27H29N2O6P (243974-35-8)

Conditions	Yield
With copper(II) bis(trifluoromethanesulfonate) In dichloromethane at 20℃; for 48h; Reagent/catalyst;	25%

Z-Pro-NH2 (34079-31-7) → N-benzyloxycarbonyl-L-isoglutamine (6398-06-7)

Conditions	Yield
With sodium hydroxide In 1,4-dioxane

2-oxo-propionic acid (127-17-3) + Z-Pro-NH2 (34079-31-7) → Nα-benzyloxycarbonyl-L-prolyldehydroalaninate

Conditions	Yield
With hydroquinone In benzene for 6.5h; Heating;

ethanol (64-17-5) + Z-Pro-NH2 (34079-31-7) → C15H20N2O3*BF4(1-)*H(1+)

Conditions	Yield
With triethyloxonium fluoroborate In dichloromethane for 1h; Heating;

Upstream product

• 2766-18-9 N-carbobenzoxyprolylglycine 
• 61350-60-5 (S)-benzyloxycarbonyl-proline acid chloride 
• 3304-59-4 N-benzyloxycarbonyl-L-proline p-nitrophenyl ester 
• 60433-33-2 C₁₆H₁₉NO₅ 
• 124980-30-9 N-carbobenzoxy-L-proline phenylmethyl ester 
• 501-53-1 benzyl chloroformate 
• 14030-00-3 (2S)-2-[({(2S)-1-[(benzyloxy)carbonyl]tetrahydro-1H-pyrrol-2-yl}carbonyl)amino]propanoic acid 
• 147-85-3 L-proline 
• 1148-11-4 N-Benzyloxycarbonyl-L-proline 
• 7531-52-4 L-prolinamide 

Downstream Products

• 6398-06-7 N-benzyloxycarbonyl-L-isoglutamine 
• 96308-19-9 Z-Pro-N(Boc)2 
• 63808-36-6 (2S)-2-cyanopyrrolidine-1-carboxylic acid benzyl ester 
• 7531-52-4 L-prolinamide 
• 865838-95-5 benzyl (2S)-2-((2R)-2-ethoxy-5-oxo-2,5-dihydrofuran-3-ylcarbamoyl)pyrrolidine-1-carboxylate 
• 865838-96-6 benzyl (2S)-2-((2S)-2-ethoxy-5-oxo-2,5-dihydrofuran-3-ylcarbamoyl)pyrrolidine-1-carboxylate 
• 1005796-57-5 benzyl (S,E)-2-(3-ethoxy-3-oxoprop-1-enylcarbamoyl)pyrrolidine-1-carboxylate 
• 944030-47-1 (S)-5-phenyl-2-(pyrrolidin-2-yl)-1H-imidazole 
• 871981-77-0 3-[5-(1-benzyloxycarbonyl-(2S)-pyrrolidinyl)-2H-tetrazol-2-yl]propionic acid ethyl ester 
• 1262854-85-2 C₁₅H₁₆N₂O₂S 

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