6456-74-2

Basic information

• Product Name: tert-Butyl glycinate
• Synonyms: 2-aminoacetic acid tert-butyl ester;tert-butyl 2-aminoacetate;tert-butyl 2-azanylethanoate;1tert-butyl2-aMinoacetate;DL-Glycine tert-butyl ester;tert-Butyl aminoacetate;H-Gly-OtBu-OH (Glycine Tert Butyl Ester);TERT-BUTYL GLYCINATE FOR SYNTHESIS
• CAS NO: 6456-74-2
• Molecular Formula: C₆H₁₃NO₂
• Molecular Weight: 131.17
• EINECS: 1533716-785-6
• Product Categories: Miscellaneous;Telmisartan
• Mol File: 6456-74-2.mol
• Article Data: 31

Chemical Properties

• Melting Point: 148-150 °C (decomp)
• Boiling Point: 29-31°C 2mm
• Flash Point: 29-31°C/2mm
• Appearance: White crystalline powder/Colorless Clear Liquid
• Density: 0,96 g/cm3
• Refractive Index: 1.4240
• Storage Temp.: Store at +2°C to +8°C.
• PKA: 7.36±0.29(Predicted)
• Water Solubility: Miscible with acetone and methanol. Slightly miscible with ehtanol. Immiscible with water.
• Sensitive: Air Sensitive
• BRN: 2039000
• CAS DataBase Reference: tert-Butyl glycinate(CAS DataBase Reference)
• NIST Chemistry Reference: tert-Butyl glycinate(6456-74-2)
• EPA Substance Registry System: tert-Butyl glycinate(6456-74-2)

Safety Data

• Statements: 36/38
• Safety Statements: 26-36/37/39
• TSCA: No
• Hazardous Substances Data: 6456-74-2(Hazardous Substances Data)

Usage

Uses

Glycine tert-butyl ester is used in the preparation of Schiff base by reacting with benzophenone. The resultant Schiff base undergoes asymmetric alkylation with arylmethyl bromides in the presence of O-allyl-N-(9-anthracenylmethyl)cinchonidinium bromide as chiral phase transfer catalyst to give guanidine-containing pentacyclic compound.

InChI:InChI=1/C6H13NO2/c1-6(2,3)9-5(8)4-7/h4,7H2,1-3H3

Synthetic route

tert-butyl N-(benzyloxycarbonyl)glycinate (16881-32-6) → Glycine tert-butyl ester (6456-74-2)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethanol	92%
With hydrogen; palladium on activated charcoal In ethanol
With hydrogen; palladium on activated charcoal In methanol

bromoacetic acid tert-butyl ester (5292-43-3) → Glycine tert-butyl ester (6456-74-2)

Conditions	Yield
With ammonia In diethyl ether 1.) -40 deg C, 2 h, 2.) RT, overnight;	90%
With ammonia In diethyl ether at -40℃;	87%
With ammonia at -78℃; for 48h; Inert atmosphere;	72%
With ammonia In diethyl ether at -40℃;	70%
Multi-step reaction with 2 steps 1: aq. NaN3 / acetone 2: H2 / Pd-C / methanol View Scheme

N-(9-fluorenylmethoxycarbonyl)glycine tert-butyl ester (35661-42-8) → Glycine tert-butyl ester (6456-74-2)

Conditions	Yield
With triethylamine; 1-butyl-3-methylimidazolium Tetrafluoroborate In neat (no solvent) at 25℃; Green chemistry;	82%

(2,2,2-trichloro-ethoxycarbonylamino)-acetic acid tert-butyl ester (819050-60-7) → Glycine tert-butyl ester (6456-74-2)

Conditions	Yield
With 1-methyl-1H-imidazole; zinc In ethyl acetate for 6h;	57%

tert-butyl methyl ether (1634-04-4) + glycine (56-40-6) → Glycine tert-butyl ester (6456-74-2)

Conditions	Yield
With sulfuric acid at 25℃; for 2h; Molecular sieve; chemoselective reaction;	51%

Fms-Gly-OtBu (1245735-65-2) → Glycine tert-butyl ester (6456-74-2)

Conditions	Yield
With piperidine In N,N-dimethyl-formamide at 25℃; for 0.166667h;

N-(diphenylmethylene)glycine tert-butyl ester (81477-94-3) → benzophenone (119-61-9) + Glycine tert-butyl ester (6456-74-2)

Conditions	Yield
With cesiumhydroxide monohydrate In dichloromethane; toluene

N-(diphenylmethylene)glycine tert-butyl ester (81477-94-3) → Glycine tert-butyl ester (6456-74-2)

Conditions	Yield
With cycl-isopropylidene malonate; water In ethyl acetate at 20℃; for 8h;

Glycine tert-butyl ester (6456-74-2) + benzaldehyde (100-52-7) → tert-butyl N-benzylideneglycinate (64923-12-2)

Conditions	Yield
With sodium sulfate In benzene Ambient temperature;	100%
With trimethyl orthoformate for 8h;	96%
With magnesium sulfate In benzene for 0.5h; Ambient temperature;	75%
With magnesium sulfate In benzene
Stage #1: Glycine tert-butyl ester With magnesium sulfate; triethylamine In dichloromethane at 20℃; for 1h; Stage #2: benzaldehyde In dichloromethane at 20℃;

Glycine tert-butyl ester (6456-74-2) + Z-Gly-L-Azy-Gly-OBzl (72087-11-7) → N-carbobenzyloxy-glycyl-glycine tert-butyl ester (27375-61-7) + (2S)-H-Azy-Gly-OBzl (76314-24-4)

Conditions	Yield
In dichloromethane for 24h; Ambient temperature;	A 84.8% B 100%

Glycine tert-butyl ester (6456-74-2) + 2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-methyl-thiobutyric acid S-(2-formyl-4-nitro-phenyl) ester (557095-50-8) → Fmoc-Val-Gly-OtBu

Conditions	Yield
With N-methylmaleimide In phosphate buffer; N,N-dimethyl-formamide at 20℃; for 2.5h; pH=8.0;	100%

Glycine tert-butyl ester (6456-74-2) + 4-trifluorophenylsulfonyl chloride (2991-42-6) → tert-Butyl 2-(4-(trifluoromethyl)phenylsulfonamido)acetate (959997-92-3)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 18h;	100%

4,4-dimethylpentanal (926-36-3) + Glycine tert-butyl ester (6456-74-2) → 2-[(E)-(3,3-dimethylbutylidene)amino]acetic acid tert-butyl ester (1219086-34-6)

Conditions	Yield
In dichloromethane at 20℃;	100%
In dichloromethane at 20℃;

3,3-dimethylbutyrylaldehyde (2987-16-8) + Glycine tert-butyl ester (6456-74-2) → 2-[(E)-(3,3-dimethylbutylidene)amino]acetic acid tert-butyl ester (1219086-34-6)

Conditions	Yield
In dichloromethane at 20℃;	100%
In dichloromethane at 20℃;	100%
In dichloromethane at 20℃;	100%

Glycine tert-butyl ester (6456-74-2) + (N-benzyloxycarbonyl)-L-alanine N-hydroxysuccinimide ester (3401-36-3) → tert-butyl ((benzyloxy)carbonyl)-L-alanylglycinate (13512-48-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Inert atmosphere;	100%
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Inert atmosphere;
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Inert atmosphere;

1-chloro-4-methoxyisoquinoline-3-carboxylic acid (914672-45-0) + Glycine tert-butyl ester (6456-74-2) → tert-butyl 2-(1-chloro-4-methoxyisoquinoline-3-carboxamido)acetate

Conditions

Yield

Stage #1: 1-chloro-4-methoxyisoquinoline-3-carboxylic acid With N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #2: Glycine tert-butyl ester In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #3: With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 16h; Inert atmosphere;

100%

Glycine tert-butyl ester (6456-74-2) + C46H51N5O10 → C52H62N6O11

Conditions	Yield
With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at -5 - 20℃; Temperature;	100%

Glycine tert-butyl ester (6456-74-2) + C69H75N5O18 → C75H86N6O19

Conditions	Yield
Stage #1: Glycine tert-butyl ester; C69H75N5O18 With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate at 0℃; for 0.333333h; Stage #2: With N-ethyl-N,N-diisopropylamine at 0℃;	100%

Glycine tert-butyl ester (6456-74-2) + C68H73N5O18 → C74H84N6O19

Conditions	Yield
Stage #1: Glycine tert-butyl ester; C68H73N5O18 With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide	100%

Glycine tert-butyl ester (6456-74-2) + (2'S,5R)-1-(1'-oxo-2'-phenylmethylpropyl)-3,3,5-trimethylpyrrolidin-2-one (155956-28-8) → (2S)-N-tert-butoxycarbonylmethyl-2-phenylmethylpropanamide

Conditions	Yield
for 120h;	99%
at 20℃; for 120h;	99%

Glycine tert-butyl ester (6456-74-2) + 2,2,2-Trichloroethyl chloroformate (17341-93-4) → (2,2,2-trichloro-ethoxycarbonylamino)-acetic acid tert-butyl ester (819050-60-7)

Conditions	Yield
With pyridine In tetrahydrofuran at 0 - 20℃;	99%

BTZO-2 (501375-54-8) + Glycine tert-butyl ester (6456-74-2) → tert-butyl ({3-[6-(4-Oxo-4H-1,3-benzothiazin-2-yl)-2-pyridyl]propanoyl }amino)acetate

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 17h;	99%

Glycine tert-butyl ester (6456-74-2) + benzyl chloroformate (501-53-1) → benzyloxycarbonyl-amino acetic acid tert-butyl ester

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 3h;	99%

2,2-dimethyl-4-oxobutyronitrile (18240-73-8) + Glycine tert-butyl ester (6456-74-2) → tert-butyl (E)-2-(3-cyano-3-methylbutylideneamino)acetate

Conditions	Yield
In dichloromethane at 20℃;	98.8%

Glycine tert-butyl ester (6456-74-2) + Allyloxycarbonylamino-acetic acid (3aR,5R,6S,6aR)-5-dimethylaminomethyl-2,2-dimethyl-tetrahydro-furo[2,3-d][1,3]dioxol-6-yl ester (145147-49-5) → Aloc-Gly-Gly-OtBu (145147-53-1)

Conditions	Yield
lithium bromide In dichloromethane at 20℃; for 24h;	98%
lithium bromide In dichloromethane at 20℃; for 24h; Rate constant; other carbohydrate ester of N-protected amino acids, other amino acid esters; uncatalyzed reaction;	98%

Glycine tert-butyl ester (6456-74-2) + 6-methyl-2,4-pyrimidine-diyl dibenzoate (155632-06-7) → 6-Methyluracil (626-48-2) + hippuric acid tert-butyl ester (19811-56-4)

Conditions	Yield
In dichloromethane for 0.5h; Heating;	A n/a B 98%

Glycine tert-butyl ester (6456-74-2) + (1S)-N,N-bis(1-methylethyl)-7,7-dimethyl-2-thioxobicyclo[2.2.1]heptane-1-methanesulfonamide (213532-59-3) → (1S)-1,1-dimethylethyl 2-(N,N-bis(1-methylethyl)-7,7-dimethyl-1-methanesulfonamidobicyclo[2.2.1]hept-2-ylideneamino)ethanoate

Conditions	Yield
In toluene for 48h; Heating;	98%

Benzophenone imine (1013-88-3) + Glycine tert-butyl ester (6456-74-2) → N-(diphenylmethylene)glycine tert-butyl ester (81477-94-3)

Conditions	Yield
In dichloromethane at 20℃; for 24h;	98%

Glycine tert-butyl ester (6456-74-2) + (2R,3S)-3-endo-benzyloxycarbonyl-bicyclo[2.2.1]hept-5-ene-2-endo-carboxylic acid (581100-26-7) → (2S,3R)-3-endo-(1-tert-butoxycarbonyl-methylcarbamoyl)bicyclo[2.2.1]hept-5-ene-2-endo-carboxylic acid benzyl ester

Conditions	Yield
With dmap; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 0 - 20℃; for 13h;	98%

Upstream product

• 540-88-5 acetic acid tert-butyl ester 
• 56-40-6 glycine 
• 1245735-65-2 Fms-Gly-OtBu 
• 111652-20-1 N-(tert-butoxycarbonyl)glycine tert-butyl ester 
• 406-74-6 tert-butyl α-fluoroacetate 
• 81477-94-3 N-(diphenylmethylene)glycine tert-butyl ester 
• 35661-42-8 N-(9-fluorenylmethoxycarbonyl)glycine tert-butyl ester 
• 1634-04-4 tert-butyl methyl ether 
• 27532-96-3 glycine tert-butyl ester hydrochloride 
• 627-51-0 divinyl sulfide 
• 107-59-5 tert-Butyl chloroacetate 
• 78-84-2 isobutyraldehyde 
• 819050-60-7 (2,2,2-trichloro-ethoxycarbonylamino)-acetic acid tert-butyl ester 
• 5292-43-3 bromoacetic acid tert-butyl ester 

Downstream Products

• 100-02-7 4-nitro-phenol 
• 27375-61-7 N-carbobenzyloxy-glycyl-glycine tert-butyl ester 
• 16881-32-6 tert-butyl N-(benzyloxycarbonyl)glycinate 
• 77280-64-9 {(2-Benzyloxycarbonylamino-3-phenyl-propionyl)-[cyclohexylcarbamoyl-(9H-fluoren-9-yl)-methyl]-amino}-acetic acid tert-butyl ester 
• 19811-56-4 hippuric acid tert-butyl ester 
• 155407-44-6 2-(4-Bromo-2-fluoro-benzyl)-4-[(tert-butoxycarbonylmethyl-carbamoyl)-methyl]-6-fluoro-1,3-dioxo-1,2,3,4-tetrahydro-isoquinoline-4-carboxylic acid methyl ester 
• 2697-34-9 tert-butyl 2-(2-(((benzyloxy)carbonyl)amino)propanamido)acetate 
• 23358-34-1 Z-Phe-Gly-OtBu 
• 3236-19-9 N-Z-Ile-Gly-OC(CH₃)3 
• 63948-53-8 Z-Tyr(-Bzl)-Gly-OtBu 
• 23358-34-1 Benzyloxycarbonyl-DL-phenylalanyl-glycin-tert.-butylester 
• 139727-45-0 (1''S,3''S,5''R)-2-<<3''--6-methyl-(2''Z)-<(trimethylsilyl)methylene>cyclohexyl>ethyl>-2,5,5-trimethyl-1,3-dioxane 
• 191151-92-5 {(R)-2-Benzyloxycarbonylamino-3-[(R)-2-benzyloxycarbonylamino-2-(tert-butoxycarbonylmethyl-carbamoyl)-ethyldisulfanyl]-propionylamino}-acetic acid tert-butyl ester 
• 195257-35-3 [(1S,4R)-1-Cyclohexylsulfamoylmethyl-7,7-dimethyl-bicyclo[2.2.1]hept-(2E)-ylideneamino]-acetic acid tert-butyl ester 

Relevant articles and documents

Preparation method of tert-butyl glycine

The invention discloses a preparation method of tert-butyl glycine, and belongs to the technical field of organic synthesis. The raw materials are easily available, the process is simple, the process is simple, the reaction conditions are mild, the requirement for equipment is low, the total yield is up to 85 - 93%, and a significant amount of double-substituted by-products are effectively avoided in the direct reaction with ammonia in the traditional process.

Single Electron Transfer-Induced Selective α-Oxygenation of Glycine Derivatives

Modification of amino acids is an important strategy in organic and bioorganic chemistry. In contrast to common side-chain functionalization, backbone modification is much less explored. Especially glycine units seem to be attractive and versatile since a wide range of functionality can be potentially introduced. We report here oxidative modification of glycinates that are stable and enable further functionalization. Selective glycinate enolate oxidation by TEMPO or a FeCp2PF6/TEMPO reagent combination provides stable alkoxyamines in good to excellent yields. The methodology is expanded to glycine-containing dipeptides demonstrating selective oxygenation at the glycine unit. The orthogonal reactivity potential of oxygenated glycines for transformation to other amino acid derivatives is explored.

Multicomponent synthesis of pyroglutamic acid derivatives: Via Knoevenagel-Michael-hydrolysis-lactamization-decarboxylation (KMHL-D) sequence

A novel and practical method for the synthesis of 3-substituted pyroglutamic acid derivatives is described. One pot multicomponent reaction of Meldrum's acid, aldehyde and Schiff's base followed an unprecedented chemoselective Knoevenagel-Michael-hydrolysis-lactamization domino sequence to afford 4-carboxy 3-substituted pyroglutamic acid derivatives under mild conditions. A carboxy intermediate formed appears to accelerate its own formation. The generality of the synthesis is exemplified by the use of a wide variety of aldehydes including enolizable aliphatic aldehydes, while substrates are stable under reaction conditions.