396731-40-1

Basic information

• Product Name: 3,5-Dioxo-piperidine-1-carboxylicacidtert-butylester
• Synonyms: 3,5-Dioxo-piperidine-1-carboxylicacidtert-butylester;1-Piperidinecarboxylic acid, 3,5-dioxo-, 1,1-diMethylethyl ester
• CAS NO: 396731-40-1
• Molecular Formula: C₁₀H₁₅NO₄
• Molecular Weight: 213.2304
• Mol File: 396731-40-1.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 346.2±32.0 °C(Predicted)
• Appearance: /
• Density: 1.199±0.06 g/cm3(Predicted)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 9.72±0.20(Predicted)
• CAS DataBase Reference: 3,5-Dioxo-piperidine-1-carboxylicacidtert-butylester(CAS DataBase Reference)
• NIST Chemistry Reference: 3,5-Dioxo-piperidine-1-carboxylicacidtert-butylester(396731-40-1)
• EPA Substance Registry System: 3,5-Dioxo-piperidine-1-carboxylicacidtert-butylester(396731-40-1)

Safety Data

• Hazardous Substances Data: 396731-40-1(Hazardous Substances Data)

Usage

Uses

3,5-Dioxo-piperidine-1-carboxylicacidtert-butylester can be used as organic synthesis intermediate and pharmaceutical intermediate, mainly used in laboratory research and development process and chemical production process.

Synthesis

To a cooled (5 °C) and stirred mixture of potassium 2-methyl-2-propoxide (29.7 g,0.27 mol) was added a solution of ethyl [A/-((1,1-dimethylethoxy)carbonyl),A/-(2-oxopropyl)]glycinate (65 g, 0.25 mol) in ethyl ether (200 ml) over a period of 1.5 h. The re- sulting mixture was stirred for an additional 3 h, and the formed precipitate was filtered offand washed with ethyl ether (2 x 100 ml). The solid was dissolved in water (150 ml), andacetic acid was added to adjust the pH to 4. The product was filtered, washed with water (2x 50 ml) and air dried to furnish 1 -[(1,1 -dimethylethoxy)carbonyl]-3,5-dioxopiperidine (28 g,52 %).>xxN'TOHPLC-MS: m/z: 158 (M+H-56).1H-NMR (DMSO-d6): 81.48 (9H, s), 4.03 (4H, s), 5.38 (1 H, s).

Synthetic route

ethyl 2-(tert-butoxycarbonyl(2-oxopropyl)amino)acetate (873190-14-8) → tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1)

Conditions	Yield
With potassium tert-butylate In diethyl ether at 5℃; for 4.5h;	52%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 4-bromo-3,5-dioxopiperidine-1-carboxylate (478624-67-8)

Conditions	Yield
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In tetrachloromethane at 10 - 15℃; for 1.5h;	100%
With N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) In dichloromethane at 0℃; for 2h; Inert atmosphere;	100%
With N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) In dichloromethane at 0℃; for 2h; Inert atmosphere;	100%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + toluene-4-sulfonic acid hydrazide (1576-35-8) → tert-butyl 5-[(4-methylphenyl)hydrazinesulfonyl]-3-oxo-1,2,3,6-tetrahydropyridine-1-carboxylate

Conditions	Yield
With acetic acid In water at 0 - 25℃; for 48h; Inert atmosphere;	75%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + p-carboxybenzenesulfonyl azide (17202-49-2) → 1,1-dimethylethyl 4-azo-3,5-dioxo-1-piperidinecarboxylate

Conditions	Yield
With triethylamine In acetonitrile at 0 - 20℃; for 1.16667h;	72.3%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + phenyl isothiocyanate (103-72-0) → tert-butyl 5-hydroxy-3-oxo-4-(phenylcarbamothioyl)-3,6-dihydropyridine-1(2H)-carboxylate

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 0 - 20℃; for 16h;	54%

3-nitro-4-pyridinecarboxaldehyde (153813-70-8) + tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 4-oxo-1,3,5,10-tetrahydropyrido[3,4-b][1,7]naphthyridine-2-carboxylate

Conditions	Yield
With iron; acetic acid at 50℃; for 3h;	40%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 2-nitro-benzaldehyde (552-89-6) → tert-butyl 4-oxo-1,3-dihydrobenzo[b][1,7]naphthyridine-2-carboxylate

Conditions	Yield
With iron; acetic acid at 50℃; for 1h;	37%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-aminopyrazole (1820-80-0) + 3-(4-chlorophenoxy)benzaldehyde (69770-20-3) + trifluoroacetic acid (76-05-1) → 4-[3-(4-chlorophenoxy)phenyl]-2,4,6,7,8,9-hexahydropyrazolo[3,4-9b]-1,7-naphthyridin-5-one trifluoroacetic acid

Conditions	Yield
Stage #1: tert-butyl 3,5-dioxopiperidine- 1-carboxylate; 3-aminopyrazole; 3-(4-chlorophenoxy)benzaldehyde In ethanol for 0.5h; Reflux; Stage #2: trifluoroacetic acid In dichloromethane at 20℃; for 1h;	31%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + acetic anhydride (108-24-7) → C12H17NO5

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 22℃; for 17h;	28%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 1-isothiocyanato-4-methylbenzene (622-59-3) → tert-butyl 5-hydroxy-4-[(4-methylphenyl)carbamothioyl]-3-oxo-3,6-dihydropyridine-1(2H)-carboxylate

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 16h;	26%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + (4-fluorobenzyl)magnesium chloride (1643-73-8) → tert-butyl 3-(4-fluorobenzyl)-3-hydroxy-5-oxopiperidine-1-carboxylate

Conditions	Yield
Stage #1: tert-butyl 3,5-dioxopiperidine- 1-carboxylate With sodium hydride In tetrahydrofuran; mineral oil for 0.5h; Inert atmosphere; Stage #2: (4-fluorobenzyl)magnesium chloride In tetrahydrofuran; mineral oil at 20 - 60℃; for 4h;	25%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 4-fluorophenyl isothiocyanate (1544-68-9) → tert-butyl 4-[(4-fluorophenyl)carbamothioyl]-5-hydroxy-3-oxo-3,6-dihydropyridine-1(2H)-carboxylate

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 16h;	24%

2-pyridylisothiocyanate (52648-45-0) + tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 5-hydroxy-3-oxo-4-(pyridin-2-ylcarbamothioyl)-3,6-dihydropyridine-1(2H)-carboxylate

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 0 - 20℃; for 16h;	10%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + N,N-dimethyl-formamide dimethyl acetal (4637-24-5) → tert-butyl 4-((dimethylamino)methylene)-3,5-dioxopiperidine-1-carboxylate (478623-90-4)

Conditions	Yield
at 20 - 80℃; for 3.5h;
In toluene at 50 - 80℃; for 4h;

2-chloroethanal (107-20-0) + tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → 1,1-dimethylethyl 2-hydroxy-2,3,4,7-tetrahydro-4-oxo-furo[2,3-c]pyridine-6(5H)-carboxylate (478625-45-5)

Conditions	Yield
Stage #1: 2-chloroethanal; tert-butyl 3,5-dioxopiperidine- 1-carboxylate With sodium hydrogencarbonate In tetrahydrofuran; water at 0 - 20℃; Stage #2: With hydrogenchloride In tetrahydrofuran; water

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-aminopyrazole (1820-80-0) + trifluoroacetic acid (76-05-1) + 5-((1H-benzo[d]imidazol-2-yl)thio)furan-2-carbaldehyde (39689-08-2) → 4-[5-(1H-benzimidazol-2-ylsulfanyl)furan-2-yl]-2,4,6,7,8,9-hexahydropyrazolo[3,4-b]-1,7-naphtyridin-5-one trifluoroacetic acid

Conditions	Yield
Stage #1: tert-butyl 3,5-dioxopiperidine- 1-carboxylate; 3-aminopyrazole; 5-((1H-benzo[d]imidazol-2-yl)thio)furan-2-carbaldehyde In ethanol for 0.5h; Reflux; Stage #2: trifluoroacetic acid In dichloromethane at 20℃; for 1h;

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-aminopyrazole (1820-80-0) + 2-Fluorobenzaldehyde (446-52-6) + trifluoroacetic acid (76-05-1) → 4-(2-fluorophenyl)-2,4,6,7,8,9-hexahydropyrazolo[3,4-b]-1,7-naphtyridin-5-one trifluoroacetic acid

Conditions	Yield
Stage #1: tert-butyl 3,5-dioxopiperidine- 1-carboxylate; 3-aminopyrazole; 2-Fluorobenzaldehyde In ethanol for 0.5h; Reflux; Stage #2: trifluoroacetic acid In dichloromethane at 20℃; for 1h;

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-aminopyrazole (1820-80-0) + trifluoroacetic acid (76-05-1) + 3-(3,5-dichloro-phenoxy)-benzaldehyde → 4-[3-(3,5-dichlorophenoxy)phenyl]-2,4,6,7,8,9-hexahydropyrazolo[3,4-b]-1,7-naphtyridin-5-one trifluoroacetic acid

Conditions	Yield
Stage #1: tert-butyl 3,5-dioxopiperidine- 1-carboxylate; 3-aminopyrazole; 3-(3,5-dichloro-phenoxy)-benzaldehyde In ethanol for 0.5h; Reflux; Stage #2: trifluoroacetic acid In dichloromethane at 20℃; for 1h;

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-aminopyrazole (1820-80-0) + 3-Phenoxybenzaldehyde (39515-51-0) + trifluoroacetic acid (76-05-1) → 4-(3-phenoxyphenyl)-2,4,6,7,8,9-hexahydropyrazolo[3,4-b]-1,7-naphtyridin-5-one trifluoroacetic acid

Conditions	Yield
Stage #1: tert-butyl 3,5-dioxopiperidine- 1-carboxylate; 3-aminopyrazole; 3-Phenoxybenzaldehyde In ethanol for 0.5h; Reflux; Stage #2: trifluoroacetic acid In dichloromethane at 20℃; for 1h;

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-aminopyrazole (1820-80-0) + 3-(4-methoxyphenoxy)benzaldehyde (62373-80-2) + trifluoroacetic acid (76-05-1) → 4-[3-(4-methoxyphenoxy)phenyl]-2,4,6,7,8,9-hexahydropyrazolo[3,4-b]-1,7-naphtyridin-5-one trifluoroacetic acid

Conditions	Yield
Stage #1: tert-butyl 3,5-dioxopiperidine- 1-carboxylate; 3-aminopyrazole; 3-(4-methoxyphenoxy)benzaldehyde In ethanol for 0.5h; Reflux; Stage #2: trifluoroacetic acid In dichloromethane at 20℃; for 1h;

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-aminopyrazole (1820-80-0) + trifluoroacetic acid (76-05-1) + 3-(3,4-dichlorophenoxy)benzaldehyde (79124-76-8) → 4-[3-(3,4-dichlorophenoxy)phenyl]-2,4,6,7,8,9-hexahydropyrazolo[3,4-b]-1,7-naphtyridin-5-one trifluoroacetic acid

Conditions	Yield
Stage #1: tert-butyl 3,5-dioxopiperidine- 1-carboxylate; 3-aminopyrazole; 3-(3,4-dichlorophenoxy)benzaldehyde In ethanol for 0.5h; Reflux; Stage #2: trifluoroacetic acid In dichloromethane at 20℃; for 1h;

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-amino-2-ethoxycarbonylpyrrole hydrochloride + 5-((1H-benzo[d]imidazol-2-yl)thio)furan-2-carbaldehyde (39689-08-2) → 9-[5-(1H-benzimidazol-2-ylsulfanyl)uran-2-yl]-8-oxo-4,5,6,7,8,9-hexahydro-2H-pyrrolo[3,4-b]-1,7-naphthyridine-3-carboxylic acid ethyl ester hydrochloride

Conditions	Yield
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / ethanol / 0.5 h / Reflux 2: hydrogenchloride / 1,4-dioxane / 4 h View Scheme

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-amino-2-ethoxycarbonylpyrrole hydrochloride + 5-((1H-benzo[d]imidazol-2-yl)thio)furan-2-carbaldehyde (39689-08-2) → C29H29N5O6S

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In ethanol for 0.5h; Reflux;

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-amino-2-ethoxycarbonylpyrrole (252932-48-2) + 5-((1H-benzo[d]imidazol-2-yl)thio)furan-2-carbaldehyde (39689-08-2) → O6-tert-butyl O3-ethyl 9-[5-(1H-benzimidazol-2-ylsulfanyl)-2-furyl]-8-oxo-4,5,7,9-tetrahydro-2H-pyrrolo[3,4-b]-1,7-naphthyridine-3,6-dicarboxylate

Conditions	Yield
In butan-1-ol for 2h; Reflux;	6.9 g

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 2-amino-7-oxo-6,7-dihydro-4H-thiazolo[4,5-c]pyridine-5-carboxylate (478624-69-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2: triethylamine / methanol / 5.5 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1.1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2.1: methanol / 0.5 h / 20 °C / Inert atmosphere 2.2: 5 h / Reflux View Scheme

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 2-chloro-7-oxo-4,6-dihydrothiazolo[4,5-c]pyridine-5-carboxylate

Conditions	Yield
Multi-step reaction with 3 steps 1.1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2.1: triethylamine / methanol / 5.5 h / 20 °C / Inert atmosphere 3.1: isopentyl nitrite / acetonitrile / 0.17 h / 20 °C / Inert atmosphere 3.2: 5 h / -20 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2.1: methanol / 0.5 h / 20 °C / Inert atmosphere 2.2: 5 h / Reflux 3.1: isopentyl nitrite / acetonitrile / 0.17 h / -20 °C / Inert atmosphere 3.2: 5 h / -20 - 20 °C View Scheme

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 2-methoxy-7-oxo-6,7-dihydro-4H-thiazolo[4,5-c]pyridine-5-carboxylate

Conditions	Yield
Multi-step reaction with 4 steps 1.1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2.1: triethylamine / methanol / 5.5 h / 20 °C / Inert atmosphere 3.1: isopentyl nitrite / acetonitrile / 0.17 h / 20 °C / Inert atmosphere 3.2: 5 h / -20 - 20 °C / Inert atmosphere 4.1: methanol / -78 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2.1: methanol / 0.5 h / 20 °C / Inert atmosphere 2.2: 5 h / Reflux 3.1: isopentyl nitrite / acetonitrile / 0.17 h / -20 °C / Inert atmosphere 3.2: 5 h / -20 - 20 °C 4.1: sodium methylate / methanol / 0.75 h / -78 - 20 °C / Inert atmosphere View Scheme

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 3-methyl-2,7-dioxo-2,3,6,7-tetrahydro-4H-thiazolo[4,5-c]pyridine-5-carboxylate

Conditions

Yield

Multi-step reaction with 5 steps 1.1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2.1: triethylamine / methanol / 5.5 h / 20 °C / Inert atmosphere 3.1: isopentyl nitrite / acetonitrile / 0.17 h / 20 °C / Inert atmosphere 3.2: 5 h / -20 - 20 °C / Inert atmosphere 4.1: methanol / -78 - 20 °C / Inert atmosphere 5.1: pyridine / 0.5 h / 90 °C / Microwave irradiation 5.2: 3 h / 0 - 20 °C View Scheme

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 7-hydroxy-3-methyl-2-oxo-2,3,6,7-tetrahydro-4H-thiazolo[4,5-c]pyridine-5-carboxylate

Conditions

Yield

Multi-step reaction with 6 steps 1.1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2.1: triethylamine / methanol / 5.5 h / 20 °C / Inert atmosphere 3.1: isopentyl nitrite / acetonitrile / 0.17 h / 20 °C / Inert atmosphere 3.2: 5 h / -20 - 20 °C / Inert atmosphere 4.1: methanol / -78 - 20 °C / Inert atmosphere 5.1: pyridine / 0.5 h / 90 °C / Microwave irradiation 5.2: 3 h / 0 - 20 °C 6.1: sodium tetrahydroborate / methanol / 1 h / 0 °C / Inert atmosphere View Scheme

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 7-[allyloxy-(2-nitro-benzenesulfonyl)-amino]-3-methyl-2-oxo-2,3,6,7-tetrahydro-4H-thiazolo[4,5-c]pyridine-5-carboxylate

Conditions

Yield

Multi-step reaction with 7 steps 1.1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2.1: triethylamine / methanol / 5.5 h / 20 °C / Inert atmosphere 3.1: isopentyl nitrite / acetonitrile / 0.17 h / 20 °C / Inert atmosphere 3.2: 5 h / -20 - 20 °C / Inert atmosphere 4.1: methanol / -78 - 20 °C / Inert atmosphere 5.1: pyridine / 0.5 h / 90 °C / Microwave irradiation 5.2: 3 h / 0 - 20 °C 6.1: sodium tetrahydroborate / methanol / 1 h / 0 °C / Inert atmosphere 7.1: triphenylphosphine; di-tert-butyl-diazodicarboxylate / toluene / 4 h / 20 °C / Inert atmosphere View Scheme

Upstream product

• 873190-14-8 ethyl 2-(tert-butoxycarbonyl(2-oxopropyl)amino)acetate 

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