29588-88-3

Basic information

• Product Name: PHT-ILE-OH
• Synonyms: PHTHALOYL-L-ISOLEUCINE;PHT-ILE-OH;PHTHALYL-L-ISOLEUCINE;Pht-lle-OH;(2S,3S)-2-(1,3-dioxoisoindolin-2-yl)-3-methylpentanoic acid;N-Phthaloyl-L-isoleucine;Pht-L-Ile-OH;Pht-Ile
• CAS NO: 29588-88-3
• Molecular Formula: C₁₄H₁₅NO₄
• Molecular Weight: 261.27
• Mol File: 29588-88-3.mol
• Article Data: 16

Chemical Properties

• Melting Point: 123-125℃
• Appearance: /
• Density: 1.311
• Storage Temp.: Store at 0°C
• CAS DataBase Reference: PHT-ILE-OH(CAS DataBase Reference)
• NIST Chemistry Reference: PHT-ILE-OH(29588-88-3)
• EPA Substance Registry System: PHT-ILE-OH(29588-88-3)

Safety Data

• Hazardous Substances Data: 29588-88-3(Hazardous Substances Data)

Usage

General Description

PHT-ILE-OH is a chemical compound often used in the field of organic synthesis. It is a derivative of 1,3,4,6,7,8-hexahydro-2H-pyrrolo[3,4-g]indazole, containing an isoleucine residue and a hydroxyl group. PHT-ILE-OH has potential applications in drug discovery, pharmaceutical research, and in the development of new materials due to its unique structure and properties. PHT-ILE-OH may be used as a building block for the synthesis of various organic molecules and can also be investigated for its potential biological activities and pharmacological properties. Further research and exploration of PHT-ILE-OH may lead to the discovery of new compounds and applications in different fields of science and technology.

Synthetic route

phthalic anhydride (85-44-9) + L-isoleucine (73-32-5) → N-phthaloyl-L-isoleucine (29588-88-3)

Conditions	Yield
at 135℃;	100%
at 140℃; for 0.166667h;	99%
With triethylamine Inert atmosphere;	98%

benzyl (2S,3S)-3-methyl-2-phthalimido-pentanoate (42406-41-7) → N-phthaloyl-L-isoleucine (29588-88-3)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethanol	99%

L-isoleucine hydrochloride (17694-98-3) + methyl 2-((succinimidooxyl)carbonyl)benzoate (438470-19-0) → N-phthaloyl-L-isoleucine (29588-88-3)

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃; for 4h;	81%

L-isoleucine (73-32-5) + N-ethoxycarbonylphthalimide (22509-74-6) → N-phthaloyl-L-isoleucine (29588-88-3)

Conditions	Yield
With sodium carbonate In water	40%
Stage #1: L-isoleucine; N-ethoxycarbonylphthalimide With sodium carbonate In water at 20℃; for 3h; Stage #2: With hydrogenchloride In water at 0℃; pH=1-2;
With sodium carbonate In water at 20℃; for 5h;

Monomethyl phthalate (4376-18-5) + diethyl-<β chloride ethyl>-amine → N-phthaloyl-L-isoleucine (29588-88-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 98 percent / DCC / 1,2-dimethoxy-ethane / 6 h / 0 °C 2: 81 percent / aq. K2CO3 / acetonitrile / 4 h / 20 °C View Scheme

Monomethyl phthalate (4376-18-5) + alkali → N-phthaloyl-L-isoleucine (29588-88-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) thionyl chloride, DMF, 3.) triethylamine / 1.) reflux, 1 h, 2.) benzene, 3.) THF, 0 deg C, 2 h 2: 99 percent / H2 / 10percent Pd/C / ethanol View Scheme
Multi-step reaction with 3 steps 1: 1.) thionyl chloride, DMF, 3.) triethylamine / 1.) reflux, 1 h, 2.) benzene, 3.) THF, 0 deg C, 2 h 2: 88 percent / Bu4NBr, 5percent NaOH / CH2Cl2; H2O / 1.17 h 3: 99 percent / H2 / 10percent Pd/C / ethanol View Scheme

benzyl (2S,3S)-N-<2-(methoxycarbonyl)-benzoyl>-2-amino-3-methyl-pentanoate (157919-58-9) → N-phthaloyl-L-isoleucine (29588-88-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 88 percent / Bu4NBr, 5percent NaOH / CH2Cl2; H2O / 1.17 h 2: 99 percent / H2 / 10percent Pd/C / ethanol View Scheme

methanol (67-56-1) + N-phthaloyl-L-isoleucine (29588-88-3) → (2S,3S)-N-phthaloylisoleucine methyl ester (137649-35-5)

Conditions	Yield
With hydrogenchloride at 10℃; for 4h;	99%
With hydrogenchloride at 10℃;	98%

N-phthaloyl-L-isoleucine (29588-88-3) → (2S,3S)-2-(1,3-dioxoisoindolin-2-yl)-3-methylpentanoyl chloride (126926-31-6)

Conditions	Yield
With thionyl chloride for 1h; Ambient temperature;	94%
With thionyl chloride In dichloromethane for 5h; Heating;	88%
With thionyl chloride In toluene Reflux; Schlenk technique;

rhodium(II) acetate dimer + N-phthaloyl-L-isoleucine (29588-88-3) + ethyl acetate (141-78-6) → tetrakis[N-phthaloyl-(S)-iso-leucinate]bis(ethyl acetate)

Conditions	Yield
Stage #1: rhodium(II) acetate dimer; N-phthaloyl-L-isoleucine In chlorobenzene for 3h; Inert atmosphere; Reflux; Stage #2: ethyl acetate In hexane Inert atmosphere;	83%

N-phthaloyl-L-isoleucine (29588-88-3) + 1-(4-tert-butylbenzyl)piperazine (956-61-6) → 2-((2S,3S)-1-(4-(4-(tert-butyl)benzyl)piperazin-1-yl)-3-methyl-1-oxopentan-2-yl) isoindoline-1,3-dione

Conditions	Yield
Stage #1: N-phthaloyl-L-isoleucine With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; for 0.25h; Stage #2: With benzotriazol-1-ol In dichloromethane at 0℃; for 0.25h; Stage #3: 1-(4-tert-butylbenzyl)piperazine In dichloromethane at 20℃; for 24h;	80%

N-phthaloyl-L-isoleucine (29588-88-3) + C16H30N2OSi → C30H43N3O4Si

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	79%

N-phthaloyl-L-isoleucine (29588-88-3) + diphenyl diselenide (1666-13-3) + 2,2'-dipyridyl disulfide bis-N-oxide (3696-28-4) → (1SR,2S)-2-methyl-1-phenylseleno-1-phthalimido-butane

Conditions	Yield
With tributylphosphine In tetrahydrofuran at 16℃; for 0.0833333h; Irradiation;	78%

2-aminoethylpyridine (42088-91-5) + N-phthaloyl-L-isoleucine (29588-88-3) → C21H23N3O3

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	73%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;

N-phthaloyl-L-isoleucine (29588-88-3) + ethanol (64-17-5) → ethyl 2-(1,3-dioxoisoindolin-2-yl)-3-methylpentanoate (1423187-78-3)

Conditions	Yield
With sulfuric acid at 60℃; for 4h;	72.46%

N-phthaloyl-L-isoleucine (29588-88-3) + 2-(pyridin-2-yl)isopropyl amine (52568-28-2) → C22H25N3O3

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	71%

N-phthaloyl-L-isoleucine (29588-88-3) + 1-(4-bromobenzyl)piperazine (91345-62-9) → 2-((2S,3S)-1-(4-(4-bromobenzyl)piperazin-1-yl)-3-methyl-1-oxopentan-2-yl)isoindoline-1,3-dione

Conditions	Yield
Stage #1: N-phthaloyl-L-isoleucine With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; for 0.25h; Stage #2: With benzotriazol-1-ol In dichloromethane at 0℃; for 0.25h; Stage #3: 1-(4-bromobenzyl)piperazine In dichloromethane at 20℃; for 24h;	69%

N-phthaloyl-L-isoleucine (29588-88-3) + 1-(4-fluorophenylmethyl)piperazine (70931-28-1) → 2-((2S,3S)-1-(4-(4-fluorobenzyl)piperazin-1-yl)-3-methyl-1-oxopentan-2-yl)isoindoline-1,3-dione

Conditions	Yield
Stage #1: N-phthaloyl-L-isoleucine With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; for 0.25h; Stage #2: With benzotriazol-1-ol In dichloromethane at 0℃; for 0.25h; Stage #3: 1-(4-fluorophenylmethyl)piperazine In dichloromethane at 20℃; for 24h;	69%

4-(phenethyl)piperazine (5321-49-3) + N-phthaloyl-L-isoleucine (29588-88-3) → 2-((2S,3S)-3-methyl-1-oxo-1-(4-phenethylpiperazin-1-yl)pentan-2-yl)isoindoline-1,3-dione

Conditions	Yield
Stage #1: N-phthaloyl-L-isoleucine With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; for 0.25h; Stage #2: With benzotriazol-1-ol In dichloromethane at 0℃; for 0.25h; Stage #3: 4-(phenethyl)piperazine In dichloromethane at 20℃; for 24h;	67%

(2-aminomethylpyridine) (3731-51-9) + N-phthaloyl-L-isoleucine (29588-88-3) → C20H21N3O3

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	60%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;

N-phthaloyl-L-isoleucine (29588-88-3) + 1-(4-trifluoromethylbenzyl)piperazine (107890-32-4) → 2-((2S,3S)-3-methyl-1-oxo-1-(4-(4-(trifluoromethyl)benzyl)piperazin-1-yl)pentan-2-yl)isoindoline-1,3-dione

Conditions	Yield
Stage #1: N-phthaloyl-L-isoleucine With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; for 0.25h; Stage #2: With benzotriazol-1-ol In dichloromethane at 0℃; for 0.25h; Stage #3: 1-(4-trifluoromethylbenzyl)piperazine In dichloromethane at 20℃; for 24h;	59%

N-phthaloyl-L-isoleucine (29588-88-3) → (2S,3S)-2-(1,3-dioxoisoindolin-2-yl)-3-methylpentanamide (329686-65-9)

Conditions	Yield
With 1H-imidazole In tetrahydrofuran at 60℃; for 4h;	56.39%

N-phthaloyl-L-isoleucine (29588-88-3) + 4-chlorobenzaldehyde (104-88-1) → (Z)-N'-(4-chlorobenzylidene)-2-(1,3-dioxoisoindolin-2-yl)-3-methylpentanehydrazide (1637438-74-4)

Conditions	Yield
In ethanol for 4h; Reflux;	55.54%

N-phthaloyl-L-isoleucine (29588-88-3) + 3,4-dichlorobenzaldehyde (6287-38-3) → C21H19Cl2N3O3

Conditions	Yield
In ethanol for 4h; Reflux;	50.02%

N-phthaloyl-L-isoleucine (29588-88-3) + 4-methoxy-benzaldehyde (123-11-5) → (Z)-2-(1,3-dioxoisoindolin-2-yl)-N'-(4-methoxybenzylidene)-3-methylpentanehydrazide (1637437-24-1)

Conditions	Yield
In ethanol for 4h; Reflux;	48.75%

N-phthaloyl-L-isoleucine (29588-88-3) + benzaldehyde (100-52-7) → (Z)-N'-benzylidene-2-(1,3-dioxoisoindolin-2-yl)-3-methylpentanehydrazide

Conditions	Yield
In ethanol for 4h; Reflux;	42.84%

N-phthaloyl-L-isoleucine (29588-88-3) + hydrogen ethyl malonate (1071-46-1) → ethyl (5S)-5-methyl-3-oxo-4-phthalimidoheptanoate

Conditions	Yield
Stage #1: N-phthaloyl-L-isoleucine With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 16h; Inert atmosphere; Stage #2: hydrogen ethyl malonate With triethylamine; magnesium chloride In tetrahydrofuran at 0 - 20℃; for 4.5h; Inert atmosphere;	14%

N-phthaloyl-L-isoleucine (29588-88-3) + isobutyl chloroformate (543-27-1) → C19H23NO6

Conditions	Yield
With 4-methyl-morpholine In tetrahydrofuran at -20℃; for 0.166667h;

N-phthaloyl-L-isoleucine (29588-88-3) → Ethyl 3-sec-butyl-2,5-dioxo-2,3-dihydro-5H-pyrrolo<1,2-a>isoindole-1-carboxylate

Conditions	Yield
Multi-step reaction with 3 steps 1: 94 percent / SOCl2 / 1 h / Ambient temperature 2: 76 percent / tetrahydrofuran / 4 h / Heating 3: 0 h / 500 °C / 0 - 0.01 Torr View Scheme

N-phthaloyl-L-isoleucine (29588-88-3) → (4S,5S)-4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-5-methyl-3-oxo-2-(triphenyl-λ5-phosphanylidene)-heptanoic acid ethyl ester (175913-71-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 94 percent / SOCl2 / 1 h / Ambient temperature 2: 76 percent / tetrahydrofuran / 4 h / Heating View Scheme

N-phthaloyl-L-isoleucine (29588-88-3) → (2S,3S)-2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-pentanoic acid 2-thioxo-2H-pyridin-1-yl ester (157919-38-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: NMM / tetrahydrofuran / 0.17 h / -20 °C 2: Et3N, DMAP / tetrahydrofuran / 0.5 h View Scheme

N-phthaloyl-L-isoleucine (29588-88-3) → (1SR,2S)-1-deutero-2-methyl-1-phthalimido-butane

Conditions	Yield
Multi-step reaction with 4 steps 1: NMM / tetrahydrofuran / 0.17 h / -20 °C 2: Et3N, DMAP / tetrahydrofuran / 0.5 h 3: 34 percent / tetrahydrofuran / 0.08 h / 16 °C / Irradiation 4: 79 percent / Bu3SnD, AIBN / benzene / 2 h / 80 °C View Scheme

Upstream product

• 85-44-9 phthalic anhydride 
• 73-32-5 DL-isoleucine 
• 73-32-5 L-isoleucine 
• 22509-74-6 N-ethoxycarbonylphthalimide 
• 17694-98-3 L-isoleucine hydrochloride 
• 438470-19-0 methyl 2-(N-succinimidyloxycarbonyl)benzoate 
• 157919-58-9 benzyl (2S,3S)-N-<2-(methoxycarbonyl)-benzoyl>-2-amino-3-methyl-pentanoate 
• 4376-18-5 Monomethyl phthalate 
• 42406-41-7 benzyl (2S,3S)-3-methyl-2-phthalimido-pentanoate 

Relevant articles and documents

Synthesis of new amides based on N-Phthaloyl-α-Amino Acids

N-phthaloyl derivatives of aliphatic α-amino acids were synthesized using phthalanhydride under standard conditions. The optimization reaction carried out by the thermal method to obtain the amides of these N-phthaloyl amino acids resulted in transimitted rather than amidation. The target amides of N-phthaloyl-α-amino acids were obtained by acylation of the amine with the corresponding acid chloroanhydrides in dichloromethane. These results were compared with the results of a similar acylation in a non-polar solvent (benzene). The dependence of the direction of the reaction on the duration of the acylation and the amount of amine used was established. The conditions for the formation of the corresponding N-phthaloyl-α-amino acid amides and asymmetric phthalic acid diamides were found. It is noteworthy that the formation of diamides is directly proportional to the equivalent amount of amine and the duration of the reaction, which makes it possible to purposefully control the synthesis in one reactor.

Chiral sensors for determining the absolute configurations of α-amino acid derivatives

A simple strategy for configurational assignments of alpha-amino acids has been developed by comparison of the proton NMR chemical shift values of the alpha hydrogens of N-phthaloyl protected alpha-amino acids in the presence of (R)-CSA 1 and (S)-CSA 1, respectively. Highly resolved NMR spectra can be obtained directly on the mixed solution of the chiral solvating agents with N-phthaloyl protected alpha-amino acids in NMR tubes, giving well distinguishable proton signals without interference which dramatically improve the accuracy of assignment and hasten the assigning procedure. The strategy is widely applicable for varied natural and non-natural amino acids.

Enantiomerically Pure [2.2]Paracyclophane-4-thiol: A Planar Chiral Sulfur-Based Building Block Readily Available by Resolution with an Amino Acid Chiral Auxiliary

Acyl chloride of N-phthaloyl-(S)-isoleucine is an efficient chiral auxiliary for the resolution of (±)-[2.2]paracyclophane-4-thiol. A preparative protocol, based on the conversion into diastereoisomeric thiolesters and separation by two fractional crystallizations and column chromatography, was developed. Deprotection with LiAlH4 allowed isolation of the individual thiol enantiomers in good yield (～40%) and high enantiomeric purity (ee >93%). The absolute configurations were determined by comparison of the optical rotation value of the products with literature data and were confirmed by X-ray crystallography.