31140-42-8

Basic information

• Product Name: 3-BOC-AMINO-2,6-DIOXOPIPERIDINE
• Synonyms: TERT-BUTYL 2,6-DIOXOPIPERIDIN-3-YLCARBAMATE;3-BOC-AMINO-2,6-DIOXOPIPERIDINE;2,6-Dioxo-3-piperidinecarbamic acid tert-butyl ester;CarbaMic acid, (2,6-dioxo-3-piperidinyl)-, 1,1-diMethylethyl ester
• CAS NO: 31140-42-8
• Molecular Formula: C₁₀H₁₆N₂O₄
• Molecular Weight: 228.25
• Product Categories: pharmacetical
• Mol File: 31140-42-8.mol
• Article Data: 25

Chemical Properties

• Melting Point: 193.7-194.4 °C
• Boiling Point: 423 °C at 760 mmHg
• Flash Point: 209.6 °C
• Appearance: /
• Density: 1.20
• Vapor Pressure: 2.32E-07mmHg at 25°C
• Refractive Index: 1.499
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Chloroform (Slightly, Heated), DMF (Slightly), DMSO (Slightly), Methanol (Slight
• PKA: 10.78±0.20(Predicted)
• CAS DataBase Reference: 3-BOC-AMINO-2,6-DIOXOPIPERIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: 3-BOC-AMINO-2,6-DIOXOPIPERIDINE(31140-42-8)
• EPA Substance Registry System: 3-BOC-AMINO-2,6-DIOXOPIPERIDINE(31140-42-8)

Safety Data

• Hazardous Substances Data: 31140-42-8(Hazardous Substances Data)

Usage

Uses

tert-Butyl (2,6-Dioxopiperidin-3-yl)carbamate is an intermediate in the synthesis of Thalidomide-d4 (T338852), a labelled Thalidomide, which inhibits FGF-induced angiogenesis. Inhibits replication of human immunodeficiency virus type 1. Teratogenic sedative.

InChI:InChI=1/C10H16N2O4/c1-10(2,3)16-9(15)11-6-4-5-7(13)12-8(6)14/h6H,4-5H2,1-3H3,(H,11,15)(H,12,13,14)

Synthetic route

5-amino-2-(tert-butoxycarbonylamino)-5-oxo-pentanoic acid (85535-45-1) → (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8)

Conditions	Yield
With dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 80℃;	99%
With dmap; triethylamine; 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 72h;	90%
With dmap; 1,1'-carbonyldiimidazole In tetrahydrofuran for 16h; Reflux;	88%

1-[(tert-butoxy)-carbonyl-amino]propane-1,3-dicarboxylic acid (120341-33-5) → (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8)

Conditions	Yield
With 2,2,2-trifluoroacetamide; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine at 20℃;	95%
With 2,2,2-trifluoroacetamide; TEA; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane

di-tert-butyl dicarbonate (24424-99-5) + rac-α-aminoglutarimide hydrochloride (24666-56-6) → (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8)

Conditions	Yield
Stage #1: rac-α-aminoglutarimide hydrochloride With triethylamine In dichloromethane at 50℃; for 0.5h; Sealed tube; Microwave irradiation; Stage #2: di-tert-butyl dicarbonate In dichloromethane at 0℃; for 0.5h;	87%

Boc-Gln-OH (13726-85-7) → (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8)

Conditions	Yield
With dmap; 1,1'-carbonyldiimidazole In tetrahydrofuran for 17h; Heating;	76%
With dmap; 1,1'-carbonyldiimidazole In tetrahydrofuran for 24h; Heating;	76%
With dmap; 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; Inert atmosphere; Reflux;	76%

Boc-glutamine methyl ester → (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8)

Conditions	Yield
With 1-hydroxy-pyrrolidine-2,5-dione; diisopropyl-carbodiimide In tetrahydrofuran for 48h; Reflux;	66.2%

(S)-methyl 5-amino-2-(tert-butoxycarbonylamino)-5-oxopentanoate (4976-88-9) → (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8)

Conditions	Yield
With dmap; 1,1'-carbonyldiimidazole In tetrahydrofuran for 48h; Reflux;	64%

di-tert-butyl dicarbonate (24424-99-5) + 3-aminopiperidine-2,6-dione hydrochloric acid salt → (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 8h;	58%

glutamine methyl ester (1218991-05-9) → (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / water; methanol / 15 h / 20 °C 2: diisopropyl-carbodiimide; 1-hydroxy-pyrrolidine-2,5-dione / tetrahydrofuran / 48 h / Reflux View Scheme

GLUTAMINE (56-85-9, 585-21-7, 5959-95-5, 6899-04-3) → (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: thionyl chloride / 8 h / 0 °C / Reflux 2: sodium hydrogencarbonate / water; methanol / 15 h / 20 °C 3: diisopropyl-carbodiimide; 1-hydroxy-pyrrolidine-2,5-dione / tetrahydrofuran / 48 h / Reflux View Scheme

(RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) + trifluoroacetic acid (76-05-1) → (RS)-2,6-dioxopiperidin-3-yl-ammonium trifluoroacetate

Conditions	Yield
at 20℃; for 0.5h;	100%
In dichloromethane at 25℃;	99%
In dichloromethane at 20℃; for 4h;	98%

(RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → (RS)-2,6-dioxopiperidin-3-yl-ammonium trifluoroacetate

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 20℃; for 4h;	99%

(RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → rac-α-aminoglutarimide hydrochloride (24666-56-6)

Conditions	Yield
With hydrogenchloride In methanol; water for 2h;	99%

(RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → (+/-)-α-aminoglutarimide (2353-44-8)

Conditions	Yield
With water; sodium chloride for 4h; Time; Reflux;	98%
With trifluoroacetic acid In dichloromethane
With trifluoroacetic acid In dichloromethane at 0 - 20℃;
With trifluoroacetic acid In dichloromethane at 20℃;
With hydrogenchloride In tert-butyl methyl ether; water at 0℃; for 0.333333h;	9.5 g

(RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → 3-aminopiperidine-2,6-dione hydrobromide (90802-45-2)

Conditions	Yield
With hydrogen bromide; acetic acid at 20℃; for 0.5h;	98%
With hydrogen bromide; acetic acid at 20℃; for 0.5h;	98%

3-nitrophthalic acid anhydride (641-70-3) + (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → 4-NT (19171-18-7)

Conditions	Yield
With 2,2,2-trifluoroethanol at 150℃; for 2h; Microwave irradiation; Sealed tube;	95%
With sodium acetate; acetic acid for 6h; Reflux;

5-norbornene-2,3-dicarboxylic anhydride (826-62-0, 85081-15-8, 85081-16-9) + (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → 2-(2,6-dioxopiperidin-3-yl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (14166-22-4, 14166-24-6)

Conditions	Yield
With 2,2,2-trifluoroethanol at 150℃; for 2h; Microwave irradiation; Sealed tube;	94%

4-hydroxyphthalic anhydride (27550-59-0) + (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → 5-Hydroxythalidomide (64567-60-8)

Conditions	Yield
With 2,2,2-trifluoroethanol at 150℃; for 2h; Microwave irradiation; Sealed tube;	91%

phthalic anhydride (85-44-9) + (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → thalidomide (50-35-1)

Conditions	Yield
With 2,2,2-trifluoroethanol at 150℃; for 2h; Reagent/catalyst; Microwave irradiation;	91%
In 2,2,2-trifluoroethanol at 150℃; for 2h; Solvent;	91%
With sodium acetate; acetic acid for 6h; Reflux;

3-fluorophthalic anhydride (652-39-1) + (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → 2‐(2,6‐dioxopiperidin‐3‐yl)‐4‐fluoroisoindoline‐1,3‐dione

Conditions	Yield
With sodium acetate In acetic acid for 6h; Reflux;	89%
With 2,2,2-trifluoroethanol at 150℃; for 2h; Microwave irradiation; Sealed tube;	69%
With sodium acetate; acetic acid for 6h; Reflux;

3-hydroxyphthalic anhydride (37418-88-5) + (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → 4-Hydroxythalidomide (5054-59-1)

Conditions	Yield
With 2,2,2-trifluoroethanol at 150℃; for 2h; Microwave irradiation; Sealed tube;	86%

(RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) + 1,2-Cyclohexanedicarboxylic acid-anhydride (85-42-7) → cis-2-(2,6-dioxopiperidin-3-yl)hexahydro-1H-isoindole-1,3(2H)-dione (14166-19-9)

Conditions	Yield
With 2,2,2-trifluoroethanol at 150℃; for 2h; Microwave irradiation; Sealed tube;	86%

phthalic anhydride (85-44-9) + (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → 2-(2,6-dioxopiperidin-3-yl)hexahydro-1H-isoindole-1,3(2H)-dione

Conditions	Yield
In 2,2,2-trifluoroethanol at 150℃; for 2h; Microwave irradiation;	86%

(RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) + methyl iodide (74-88-4) → tert-butyl N-(1-methyl-2,6-dioxopiperidin-3-yl)carbamate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 3h;	84%
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 1.5h;	71%
Stage #1: (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 0.583333h; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃; for 2h;	66%

4-tert-butylphthalic anhydride (32703-79-0) + (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → 5-(tert-butyl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione

Conditions	Yield
With 2,2,2-trifluoroethanol at 150℃; for 2h; Microwave irradiation; Sealed tube;	83%

1,8-Naphthalic anhydride (81-84-5) + (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → 2-(2,6-dioxopiperidin-3-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (14656-93-0)

Conditions	Yield
With 2,2,2-trifluoroethanol at 150℃; for 6h; Microwave irradiation; Sealed tube;	80%

3-aminophthalic anhydride (17395-99-2) + (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → pomalidomide (19171-19-8)

Conditions	Yield
With 2,2,2-trifluoroethanol at 150℃; for 2h; Microwave irradiation; Sealed tube;	80%

4-bromophthalic anhydride (86-90-8) + (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → 5-bromo-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione (26166-92-7)

Conditions	Yield
With 2,2,2-trifluoroethanol at 150℃; for 2h; Microwave irradiation; Sealed tube;	75%

4-methylphthalic anhydride (19438-61-0) + (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → 2-(2,6-dioxopiperidin-3-yl)-5-methylisoindoline-1,3-dione (40313-92-6)

Conditions	Yield
With 2,2,2-trifluoroethanol at 150℃; for 2h; Microwave irradiation; Sealed tube;	74%

(RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) + 1,2,3,6-Tetrahydrophthalic anhydride (85-43-8) → 2-(2,6-dioxopiperidin-3-yl)-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione (14166-18-8)

Conditions	Yield
With 2,2,2-trifluoroethanol at 150℃; for 2h; Microwave irradiation; Sealed tube;	73%

formaldehyd (50-00-0) + (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → 1-hydroxymethyl-3-(tert-butoxycarbonylamino)-2,6-dioxopiperidine (1320352-96-2)

Conditions	Yield
In water for 0.5h; Inert atmosphere; Reflux;	72.9%

(RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) + trimellitic Anhydride (552-30-7) → 2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

Conditions	Yield
With 2,2,2-trifluoroethanol at 150℃; for 2h; Microwave irradiation; Sealed tube;	66%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) → tert-butyl (2,6-dioxo-1-((2-(trimethylsilyl)ethoxy)methyl)piperidin-3-yl)carbamate

Conditions	Yield
Stage #1: (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.25h; Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In N,N-dimethyl-formamide at 20℃; for 1h;	65%
Stage #1: (RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.25h; Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In N,N-dimethyl-formamide; mineral oil at 20℃; for 1h;	65%

(RS)-(2,6-dioxopiperidin-3-yl)carbamic acid tert-butyl ester (31140-42-8) + benzene-1,2-dicarboxylic acid (88-99-3) → thalidomide (50-35-1)

Conditions	Yield
With 2,2,2-trifluoroethanol at 150℃; for 2h; Microwave irradiation;	62%

Upstream product

• 4976-88-9 (S)-methyl 5-amino-2-(tert-butoxycarbonylamino)-5-oxopentanoate 
• 1218991-05-9 glutamine methyl ester 
• 56-85-9 GLUTAMINE 
• 24424-99-5 di-tert-butyl dicarbonate 
• 2686-86-4 3-aminopiperidine-2,6-dione hydrochloric acid salt 
• 24666-56-6 rac-α-aminoglutarimide hydrochloride 
• 85535-45-1 5-amino-2-(tert-butoxycarbonylamino)-5-oxo-pentanoic acid 
• 120341-33-5 1-[(tert-butoxy)-carbonyl-amino]propane-1,3-dicarboxylic acid 
• 13726-85-7 Boc-Gln-OH 

Downstream Products

• 827026-45-9 3-(4-nitro-1-oxoisoindolin-2-yl)piperidine-2,6-dione 
• 879126-98-4 Lenalidomide 
• 42472-93-5 2-(1-methyl-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione 
• 31804-66-7 6-(2,6-dioxopiperidin-3-yl)-5H-pyrrolo[3,4-b]pyridine-5,7(6H)-dione 
• 19171-19-8 pomalidomide 
• 64567-60-8 5-Hydroxythalidomide 
• 55003-81-1 2-(2,6-dioxo-3-piperidinyl)-5-nitro-1H-isoindole-1,3(2H)-dione 
• 191732-76-0 2-(2,6-dioxo-3-piperidinyl)-5-amino-1H-isoindole-1,3(2H)-dione 
• 14166-18-8 2-(2,6-dioxopiperidin-3-yl)-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione 
• 50-35-1 thalidomide 
• 19171-18-7 4-NT 
• 24666-56-6 rac-α-aminoglutarimide hydrochloride 
• 19246-22-1 Thalidomide 
• 2244520-92-9 4-fluoro-2-(1-methyl-2,6-dioxopiperidin-3-yI)-2,3-dihydro-1H-isoindole-1,3-dione 

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