78920-10-2

Basic information

• Product Name: 2(5H)-FURANONE, 5-HYDROXY-4-PROPYL-
• Synonyms: 2(5H)-FURANONE, 5-HYDROXY-4-PROPYL-;5-Hydroxy-4-propyl-2(5H)-furanone;5-hydroxy-4-n-propylfuran-2-one;5-Hydroxy-4-propyl-5H-furan-2-one;5-hydroxy-4-propylfuran-2(5H)-one;2-hydroxy-3-propyl-2H-furan-5-one
• CAS NO: 78920-10-2
• Molecular Formula: C₇H₁₀O₃
• Molecular Weight: 142.153
• Mol File: 78920-10-2.mol
• Article Data: 16

Chemical Properties

• Boiling Point: 325.76°C at 760 mmHg
• Flash Point: 152.212°C
• Appearance: /
• Density: 1.198g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.508
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Sparingly), Methanol (Slightly)
• PKA: 10.04±0.40(Predicted)
• CAS DataBase Reference: 2(5H)-FURANONE, 5-HYDROXY-4-PROPYL-(CAS DataBase Reference)
• NIST Chemistry Reference: 2(5H)-FURANONE, 5-HYDROXY-4-PROPYL-(78920-10-2)
• EPA Substance Registry System: 2(5H)-FURANONE, 5-HYDROXY-4-PROPYL-(78920-10-2)

Safety Data

• Hazardous Substances Data: 78920-10-2(Hazardous Substances Data)

Usage

General Description

5-Hydroxy-4-propyl-2(5H)-furanone is a chemical compound that is commonly used in the food and beverage industry as a flavoring agent. It is found naturally in fruits and vegetables such as strawberries and tomatoes, and is responsible for their sweet and fruity aroma. The compound is also used in the production of synthetic flavors and fragrances due to its pleasant scent and taste. Additionally, 5-Hydroxy-4-propyl-2(5H)-furanone has been studied for its potential antioxidant and anti-inflammatory properties, making it of interest for potential pharmaceutical and cosmetic applications. However, further research is needed to fully understand its potential benefits and risks.

InChI:InChI=1/C7H10O3/c1-2-3-5-4-6(8)10-7(5)9/h4,7,9H,2-3H2,1H3

Synthetic route

pentanal (110-62-3) + Glyoxilic acid (298-12-4) → 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2)

Conditions	Yield
With morpholine In n-heptane at 40.1 - 41.7℃; for 18h; Industrial scale;	96.3%
Stage #1: Glyoxilic acid With morpholine In water at 10 - 30℃; for 5h; Large scale; Stage #2: pentanal In water at 40 - 45℃; for 18h; Large scale; Stage #3: With hydrogenchloride In water at 25 - 30℃; for 4h; Large scale;	95.8%
In n-heptane; water at 10 - 45℃; for 7h; Temperature; Large scale;	92.5%

pentanal (110-62-3) → 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2)

Conditions	Yield
Stage #1: Glyoxilic acid With morpholine In n-heptane; water at 20℃; for 1h; Stage #2: pentanal In n-heptane; water at 43℃; for 20h; Stage #3: With hydrogenchloride In n-heptane; water at 20℃; for 2h;	90.8%

pentanal (110-62-3) + 2,2-dihydroxyacetic acid (563-96-2) → 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2)

Conditions	Yield
With morpholin hydrochloride In 1,4-dioxane; water 1) RT, 1 h, 2) 24 h, reflux;	70%

5-Ethoxy-4-propyl-5H-furan-2-one (78920-15-7) → 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2)

Conditions	Yield
With hydrogenchloride for 0.25h; Heating; Yield given;

5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → 4-propyl-5H-furan-2-one (21963-27-9)

Conditions	Yield
With sodium tetrahydroborate In methanol at 20℃; for 1h;	100%
With sodium tetrahydroborate In ethanol for 2h; Inert atmosphere; Large scale;	90%
With methanol; sodium tetrahydroborate at 20℃; for 1h;	90.15%
With sodium tetrahydroborate In toluene at 20℃; for 4h; Reagent/catalyst; Inert atmosphere;	80%

(S)-2-aminobutyric acid methyl ester hydrochloride + 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → methyl (2S)-2-(2-hydroxy-5-oxo-3-propyl-2,5-dihydro-1H-pyrrol-1-yl)butanoate

Conditions	Yield
With triethylamine In toluene at 20℃; for 3h; Time; Large scale;	90%

(S)-2-amino-butanamide hydrochloride (53726-14-0) + 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → (2S)-2-(2-hydroxy-5-oxo-3-propyl-2,5-dihydro-1H-pyrrole-1-yl)butanamide

Conditions	Yield
Stage #1: (S)-2-amino-butanamide hydrochloride With ammonia In isopropyl alcohol pH=9 - 10; Stage #2: 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one In isopropyl alcohol at 30 - 40℃;	88.8%
at 20℃;	65.3%

(S)-2-amino-butanamide (7324-11-0, 53726-14-0, 104652-77-9, 143164-46-9) + 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → (2S)-4,5-dehydro-(2-oxo-4-n-propyl-1-pyrrolidinyl)-2-butanamide (357338-13-7)

Conditions	Yield
With sodium tetrahydroborate; sodium hydroxide In water; isopropyl alcohol at 5 - 25℃; for 1h;	88.3%
Stage #1: (S)-2-amino-butanamide; 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one In toluene at 18℃; for 2.5h; Stage #2: With sodium hydroxide In water; toluene for 1h; Stage #3: With sodium hydroxide; acetic acid more than 3 stages;	3.4%
Stage #1: (S)-2-amino-butanamide; 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one In ethanol at 40℃; for 0.0833333h; Stage #2: With sodium tetrahydroborate; ammonia In ethanol at 40℃; for 0.166667h; Stage #3: With acetic acid In ethanol at 105℃; for 0.15h;

L-2-aminobutyric acid (1492-24-6) + 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → (S)-2-(4-propyl-1,5-dihydropyrrole-2-one)butanoic acid

Conditions	Yield
Stage #1: L-2-aminobutyric acid With sodium methylate In methanol at 0℃; for 0.5h; Stage #2: 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one In methanol at 20℃; for 0.5h; Further stages;	86.7%
Stage #1: L-2-aminobutyric acid With triethylamine In methanol at 20℃; for 0.333333h; Stage #2: 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one In methanol at 20℃; for 1.5h; Stage #3: With sodium tetrahydroborate In methanol at 0 - 10℃; for 0.333333h; Heating;	78.9%

5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) + methyl iodide (74-88-4) → methyl (Z)-3-propyl-4-oxo-2-butenoate

Conditions	Yield
Stage #1: 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one With sodium hydride In N,N,N,N,N,N-hexamethylphosphoric triamide at 0℃; for 1h; Stage #2: methyl iodide In N,N,N,N,N,N-hexamethylphosphoric triamide at 0 - 20℃; for 0.25h;	82%

L-2-aminobutanamide acetate + 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → (2S)-2-((5-oxyl-3-propyl-2,5-dihydrofuran-2-yl)amino)butanamide

Conditions	Yield
With ammonia In methanol at 30 - 40℃; for 3h; pH=9 - 10; Large scale;	80.3%

(S)-2-amino-butanamide (7324-11-0, 53726-14-0, 104652-77-9, 143164-46-9) + 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → C10H16N2O2

Conditions	Yield
In isopropyl alcohol at 30℃; for 3h;	80%

(S)-2-amino-butanamide hydrochloride (53726-14-0) + 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → (2S)-2-((5-oxyl-3-propyl-2,5-dihydrofuran-2-yl)amino)butanamide

Conditions	Yield
With ammonia In methanol at 20 - 30℃; for 2h; pH=9 - 10; Large scale;	79.8%

(S)-2-aminobutyric acid methyl ester hydrochloride (7682-18-0, 26815-92-9, 56545-22-3, 85774-09-0) + 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → methyl (2S)-2-(2-oxo-4-propyl-2,5-dihydropyrrol-1-yl)butyrate

Conditions	Yield
Stage #1: (S)-2-aminobutyric acid methyl ester hydrochloride With triethylamine In methanol at 0℃; for 0.5h; Stage #2: 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one In methanol at 20℃; for 0.5h; Further stages;	76.3%

L-2-aminobutanamide tartaric acid (868134-59-2) + 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → (2S)-2-((5-oxyl-3-propyl-2,5-dihydrofuran-2-yl)amino)butanamide

Conditions	Yield
With ammonia In isopropyl alcohol at 40 - 50℃; for 2h; pH=9 - 10; Large scale;	71.7%

1-[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methanamine (1403586-73-1) + 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → 1-[[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl]-3-propyl-2H-pyrrol-5-one

Conditions	Yield
Stage #1: 1-[2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methanamine; 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one In methanol at 20℃; for 3.5h; Stage #2: With sodium tetrahydroborate In methanol at 0℃; for 1h; Stage #3: With acetic acid In methanol at 20℃;	30%

ethanol (64-17-5) + 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → 5-Ethoxy-4-propyl-5H-furan-2-one (78920-15-7)

Conditions	Yield
With hydrogenchloride for 12h; Heating;

(S)-3-acetyl-4-isopropyl-1,3-thiazolidine-2-thione (101979-45-7) + 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → 3-((2,5-dihydro-3-propyl-5-oxo-2(R)-furanyl)acetyl)-4(S)-isopropyl-1,3-thiazolidine-2-thione

Conditions	Yield
With 1-ethyl-piperidine; tin(II) trifluoromethanesulfonate 1.) THF, from -50 to -40 deg C, 3 h, 2.) THF, from -5 to 0 deg C, 2 h; Yield given. Multistep reaction;

5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → 5-hydroxy-4-propyldihydrofuran-2-one (357338-44-4)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethyl acetate at 25℃; under 1810.02 Torr; for 2h;
With 5%-palladium/activated carbon; hydrogen In Isopropyl acetate at 20 - 25℃; under 1125.11 - 1875.19 Torr; for 2h; Solvent; Temperature; Pressure; Sealed tube;
With 5%-palladium/activated carbon; hydrogen In ethyl acetate at 25 - 30℃; under 1500.15 - 2250.23 Torr; for 2.5h; Solvent; Temperature; Pressure; Sealed tube;

5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) + N-Fmoc-2-aminobutyric amide Rink resin → brivaracetam (357336-20-0) + ((2S)-2-[(4S)-2-oxo-4-propyltetrahydro-1H-pyrrol-1-yl]butanamide)

Conditions	Yield
Multistep reaction;

5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → 5-Ethoxy-4-propyl-dihydro-furan-2-one (78920-25-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: HCl(g) / 12 h / Heating 2: 88 percent / H2 / 10percent Pd-C / ethanol / 4 h / 760 Torr View Scheme

(S)-2-amino-butanamide (7324-11-0, 53726-14-0, 104652-77-9, 143164-46-9) + 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → brivaracetam (357336-20-0) + ((2S)-2-[(4S)-2-oxo-4-propyltetrahydro-1H-pyrrol-1-yl]butanamide)

Conditions	Yield
Stage #1: (S)-2-amino-butanamide; 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one In isopropyl alcohol at 15 - 30℃; for 2h; Stage #2: With hydrogen; acetic acid; 5%-palladium/activated carbon In isopropyl alcohol at 40℃; under 150.015 - 375.038 Torr; for 20h; Product distribution / selectivity;
Stage #1: (S)-2-amino-butanamide; 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one In isopropyl alcohol at 30℃; for 2h; Stage #2: With 5%-palladium/activated carbon; hydrogen; acetic acid In isopropyl alcohol at 40℃; under 150.015 - 375.038 Torr; for 20h;

(R)-1-phenyl-ethyl-amine (3886-69-9) + 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → 5-hydroxy-1-[1-((R)-phenyl)-ethyl]-4-n-propyl-1,5-dihydro-pyrrol-2-one (1314556-95-0)

Conditions	Yield
In isopropyl alcohol at 20℃; for 1h;
In isopropyl alcohol at 20℃; for 1h;
In isopropyl alcohol at 20℃; for 1h;

(S)-1-phenyl-ethylamine (2627-86-3) + 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → 5-hydroxy-1-[1-((S)-phenyl)-ethyl]-4-n-propyl-1,5-dihydro-pyrrol-2-one (1314556-94-9)

Conditions	Yield
In isopropyl alcohol at 20℃; for 1h;
In isopropyl alcohol at 20℃; for 1h;
In isopropyl alcohol at 20℃;
In isopropyl alcohol at 20℃; for 1h;

(2S)-2-phenylglycinol (20989-17-7) + 5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → 5-hydroxy-1-(2-hydroxy-1-(S)-phenyl-ethyl)-4-n-propyl-1,5-dihydro-pyrrol-2-one (1314557-00-0)

Conditions	Yield
In methanol at 20℃; for 1h;

5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → (R,S)-3-n-propyl-4-aminobutyric acid (130912-49-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: ammonia / methanol / 1.5 h / 20 °C 2: hydrogen / palladium 10% on activated carbon / methanol / 3677.86 Torr / autoclave View Scheme

5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → (3S)-3-propyl-4-((S)-1'-phenylethylamino)butanoic acid (1314557-03-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: isopropyl alcohol / 1 h / 20 °C 2: hydrogen / palladium 10% on activated carbon / isopropyl alcohol / 2206.72 Torr / autoclave View Scheme
Multi-step reaction with 2 steps 1: isopropyl alcohol / 1 h / 20 °C 2: hydrogen / palladium 10% on activated carbon / isopropyl alcohol / 2206.72 Torr / Autoclave View Scheme
Multi-step reaction with 2 steps 1: isopropyl alcohol / 1 h / 20 °C 2: hydrogen / palladium 10% on activated carbon / isopropyl alcohol / 2206.72 Torr / Parr autoclave reactor View Scheme

5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → (3R)-3-propyl-4-((S)-1'-phenylethylamino)butanoic acid (1314557-04-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: isopropyl alcohol / 1 h / 20 °C 2: hydrogen / palladium 10% on activated carbon / isopropyl alcohol / 2206.72 Torr / autoclave View Scheme
Multi-step reaction with 2 steps 1: isopropyl alcohol / 1 h / 20 °C 2: hydrogen / palladium 10% on activated carbon / isopropyl alcohol / 2206.72 Torr / Autoclave View Scheme
Multi-step reaction with 2 steps 1: isopropyl alcohol / 1 h / 20 °C 2: hydrogen / palladium 10% on activated carbon / isopropyl alcohol / 2206.72 Torr / Parr autoclave reactor View Scheme

5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → (3R)-3-propyl-4-((R)-1'-phenylethylamino)butanoic acid (1314557-05-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: isopropyl alcohol / 1 h / 20 °C 2: hydrogen / palladium 10% on activated carbon / isopropyl alcohol / 2206.72 Torr / autoclave View Scheme
Multi-step reaction with 2 steps 1: isopropyl alcohol / 1 h / 20 °C 2: hydrogen / palladium 10% on activated carbon / isopropyl alcohol / 2206.72 Torr / Autoclave View Scheme
Multi-step reaction with 2 steps 1: isopropyl alcohol / 1 h / 20 °C 2: hydrogen / palladium 10% on activated carbon / isopropyl alcohol / 2206.72 Torr / Parr autoclave reactor View Scheme

5-hydroxy-4-n-propyl-2,5-dihydrofuran-2-one (78920-10-2) → (3S)-3-propyl-4-((R)-1'-phenylethylamino)butanoic acid (1314557-08-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: isopropyl alcohol / 1 h / 20 °C 2: hydrogen / palladium 10% on activated carbon / isopropyl alcohol / 2206.72 Torr / autoclave View Scheme
Multi-step reaction with 2 steps 1: isopropyl alcohol / 1 h / 20 °C 2: hydrogen / palladium 10% on activated carbon / isopropyl alcohol / 2206.72 Torr / Autoclave View Scheme
Multi-step reaction with 2 steps 1: isopropyl alcohol / 1 h / 20 °C 2: hydrogen / palladium 10% on activated carbon / isopropyl alcohol / 2206.72 Torr / Parr autoclave reactor View Scheme

Upstream product

• 110-62-3 pentanal 
• 563-96-2 2,2-dihydroxyacetic acid 
• 298-12-4 Glyoxilic acid 
• 78920-15-7 5-Ethoxy-4-propyl-5H-furan-2-one 

Downstream Products

• 357336-20-0 brivaracetam 
• 357336-99-3 ((2S)-2-[(4S)-2-oxo-4-propyltetrahydro-1H-pyrrol-1-yl]butanamide) 
• 1314556-95-0 5-hydroxy-1-[1-((R)-phenyl)-ethyl]-4-n-propyl-1,5-dihydro-pyrrol-2-one 
• 1314556-94-9 5-hydroxy-1-[1-((S)-phenyl)-ethyl]-4-n-propyl-1,5-dihydro-pyrrol-2-one 
• 63095-51-2 (+)-(R)-4-propyl-4,5-dihydrofuran-2(3H)-one 
• 1314557-05-5 (3R)-3-propyl-4-((R)-1'-phenylethylamino)butanoic acid 
• 1314557-08-8 (3S)-3-propyl-4-((R)-1'-phenylethylamino)butanoic acid 
• 1314557-04-4 (3R)-3-propyl-4-((S)-1'-phenylethylamino)butanoic acid 
• 1314557-03-3 (3S)-3-propyl-4-((S)-1'-phenylethylamino)butanoic acid 
• 1355169-44-6 3-propyl-4-((S)-1'-phenylethylamino)butanoic acid 
• 1315473-77-8 (S,R)-3-[(1-phenylethylamino)-methyl]-hexanoic acid hydrochloride 
• 1315473-76-7 (R,R)-3-[(1-phenylethylamino)-methyl]-hexanoic acid hydrochloride 
• 1315473-74-5 (R,S)-3-[(1-phenylethylamino)-methyl]-hexanoic acid hydrochloride 

Relevant articles and documents

Simple route to synthesize (E)-3-propyl-4-oxo-2-butenoic acid esters through the Z isomer

Esters of 3-alkyl-4-oxo-2-butenoic acid, which are very important synthons, are not equally accessible in both E and Z configurations. The (Z)-isomers can be easily obtained from 3-alkyl-4-hydroxybutenolides, in turn prepared by aminoalkylation of aliphatic aldehydes with glyoxylic acid. The (E)-isomers, on the contrary, result from laborious procedures: the condensation of aldehydes with glyoxylic acid, followed by separation from γ-hydroxybutenolide by-product and esterification, or of aldehyde enamines with glyoxylic esters, followed by Z ester by-product conversion into γ-aminobutenolide and purification. Here, we describe a straightforward route to the title compounds, applied to methyl (E)-3-propyl-4-oxo-2-butenoate, avoiding any problematic by-product or isomer chromatographic separation: pentanal and glyoxylic acid are condensed to 3-propyl-4-hydroxybutenolide, which is converted to methyl (Z)-3-propyl-4-oxo-2-butenoate and then isomerized to E ester under acidic conditions.

PROCESS FOR THE PREPARATION OF BRIVARACETAM

The present invention relates to a process for the preparation of brivaracetam, a compound of formula I and salts thereof. The present invention also relates to a compound of formula II and a compound of formula IIA, process for its preparation and conversion thereof to brivaracetam, the compound of formula I.

Asymmetric catalytic preparation method of brivaracetam

The invention discloses a preparation method of brivaracetam, which adopts cheap and accessible hydrogen as a hydrogen source, can implement asymmetric preparation of brivaracetam in a catalytic system with rhodium (I) as a metal center, and has the advantages of mild reaction conditions, simplicity, controllability, high yield, high enantioselectivity, environment friendliness, favorable atom economy, low cost and the like. In addition, the invention also provides the brivaracetam compound prepared by the method.