65284-00-6

Basic information

• Product Name: (R)-BETA-METHYL-GAMMA-BUTYROLACTONE
• Synonyms: (R)-BETA-METHYL-GAMMA-BUTYROLACTONE;(R)-β-Methyl-γ-butyrolactone;(R)-beta-Methyl-gama-butyrolactone;(R)-BETA-METHYL--BUTYROLACTONE;2(3H)-Furanone,dihydro-4-Methyl-, (4R)-;(R)-4-METHYLDIHYDROFURAN-2(3H)-ONE
• CAS NO: 65284-00-6
• Molecular Formula: C₅H₈O₂
• Molecular Weight: 100.11582
• Mol File: 65284-00-6.mol
• Article Data: 81

Chemical Properties

• Boiling Point: 206.624 °C at 760 mmHg
• Flash Point: 74.98 °C
• Appearance: /
• Density: 1.04 g/cm³
• CAS DataBase Reference: (R)-BETA-METHYL-GAMMA-BUTYROLACTONE(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-BETA-METHYL-GAMMA-BUTYROLACTONE(65284-00-6)
• EPA Substance Registry System: (R)-BETA-METHYL-GAMMA-BUTYROLACTONE(65284-00-6)

Safety Data

• Hazardous Substances Data: 65284-00-6(Hazardous Substances Data)

Usage

General Description

(R)-BETA-METHYL-GAMMA-BUTYROLACTONE is a chemical compound that belongs to the class of lactones, which are cyclic esters of hydroxy acids. It is commonly used as a precursor in the synthesis of pharmaceuticals and agrochemicals. (R)-BETA-METHYL-GAMMA-BUTYROLACTONE has potential applications in the field of organic chemistry as a chiral building block due to its unique structure. It has been studied for its potential pharmaceutical properties, including as an antiviral and anxiolytic agent. Additionally, (R)-BETA-METHYL-GAMMA-BUTYROLACTONE has been investigated for its potential use as a flavoring agent and as a precursor for the synthesis of various fine chemicals.

Synthetic route

(R)-(+)-3-methyl-4-methoxymethyloxybutanenitrile (222539-30-2) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
With sulfuric acid In acetic acid for 1.5h; Heating;	93%

1-(2-Methylpropyl) 4-hydrogen (S)-2-methylbutanedioate → (S)-3-methyl-4-butanolide (64190-48-3) + (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
With lithium borohydride In tetrahydrofuran at 50℃; for 1h;	A 69% B n/a

methyl (S)-(+)-3-methyl-5-oxohexanoate (89393-67-9) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
Stage #1: methyl (S)-(+)-3-methyl-5-oxohexanoate With 3-chloro-benzenecarboperoxoic acid In chloroform at 20℃; for 48h; Baeyer-Villager oxidation; Stage #2: With potassium hydroxide In methanol for 4h; Heating; Stage #3: With hydrogenchloride pH=3 - 4;	68%

(3R)-4-(tert-butyldimethylsilanyloxy)-3-methylbutyronitrile (172668-98-3) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
With sulfuric acid In acetic acid Heating;	60%

(S)-3-Methyl-4-<(tetrahydropyranyl)oxy>butanenitrile (110171-23-8) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
With hydrogenchloride In methanol for 7h; Heating;	46%
Multi-step reaction with 2 steps 1: aq. HCl / methanol / 4 h / Heating 2: 32.0 g / aq. NaOH / 5 h / Heating View Scheme
Multi-step reaction with 2 steps 1: aq. KOH / ethane-1,2-diol / 6 h / Heating 2: aq. HCl / 0.25 h / 100 °C View Scheme

(R)-4-(iodomethyl)dihydrofuran-2(3H)-one (88557-21-5) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
With hydrogen; calcium carbonate; Raney Ni W-7 In ethanol for 0.5h; Ambient temperature;	8.8%

methyl (R)-3-hydroxy-2-methylpropionate (72657-23-9) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

(R)-3-Methyl-4-[((E)-propenyl)oxy]-butyraldehyde (132364-20-6, 132364-47-7, 132437-73-1, 132437-98-0) → (S)-3-methyl-4-butanolide (64190-48-3) + (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
Jones oxidation; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

(R)-(+)-4-tert. butoxy-3-methylbutyric acid (60610-08-4) → (S)-3-methyl-4-butanolide (64190-48-3) + (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
With toluene-4-sulfonic acid In benzene for 1.5h; Heating; Yield given. Title compound not separated from byproducts;

trans-(R)-2-Octen-4-ol (84621-55-6) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
Multistep reaction;

(R)-4-Hydroxy-3-methyl-N-((R)-1-phenyl-ethyl)-butyramide (90897-90-8) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
With hydrogenchloride; potassium hydroxide Multistep reaction;

(2R,3S)-3,4,6-Trimethyl-2-phenyl-3,4,6,7-tetrahydro-2H-furo[3,2-f][1,4]oxazepin-5-one → (S)-3-methyl-4-butanolide (64190-48-3) + (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
In tetrahydrofuran at -100℃; Heating; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

(R)-4-Hydroxy-3-methyl-butyric acid (108772-87-8) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
With hydrogenchloride at 100℃; for 0.25h; Yield given;

(-)-ethyl (R)-(E)-3,6-dimethyl-4-heptenoate (92232-04-7) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
With sodium tetrahydroborate; ozone 1.) EtOH, CHCl3, -78 degC; Yield given. Multistep reaction;

(S)-4-Methyl-2-oxo-tetrahydro-furan-3-carboxylic acid (96540-43-1, 147139-95-5) → (S)-3-methyl-4-butanolide (64190-48-3) + (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
at 180 - 200℃; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

(R)-(+)-3-methyldihydrofuran-2,5-dione (83247-83-0) → (R)-3-methyl-γ-butyrolactone (65284-00-6) + (R)-3-methyl-dihydro-furan-2-one (55254-35-8)

Conditions	Yield
With hydrogen; magnesium sulfate; triethylamine; Ru2Cl4(DIOP)3 In toluene at 120℃; for 10h; Yield given. Title compound not separated from byproducts;

(R)-3-Methyl-4-(tetrahydro-pyran-2-yloxy)-butyramide → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
With sodium hydroxide for 5h; Cyclization; Lactonization; Hydrolysis; Heating;	32.0 g

(R)-4-hydroxy-3-methyl-butyronitrile (217189-83-8) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
Stage #1: (R)-4-hydroxy-3-methyl-butyronitrile With sodium hydroxide In ethanol Heating; Stage #2: With toluene-4-sulfonic acid In benzene Heating;

(E)-4-hydroxy-3-methylbut-2-enoic acid (44647-19-0) → (S)-3-methyl-4-butanolide (64190-48-3) + (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
Stage #1: (E)-4-hydroxy-3-methylbut-2-enoic acid With chiral ruthenium catalyst; hydrogen; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl Stage #2: With hydrogen cation Further stages.;
With Ru(OAc)2((R)-BINAP); hydrogen Title compound not separated from byproducts.;

4-methyl-2(5H)-furanone (6124-79-4) → (S)-3-methyl-4-butanolide (64190-48-3) + (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
With sodium tetrahydroborate; methyl-bis-((S)-4-phenyl-4,5-dihydro-oxazol-2-yl)-amine; cobalt(II) chloride In ethanol at 20℃; for 24h; Title compound not separated from byproducts;
With C32H12BF24(1-)*C37H44IrN2OP(1+); hydrogen In dichloromethane at 20℃; under 75007.5 Torr; for 24h; optical yield given as %ee; enantioselective reaction;

(R)-4-(tert-butyl-diphenyl-silanyloxy)-3-methyl-thiobutyric acid S-ethyl ester (917590-87-5) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran for 5h;
With tetrabutyl ammonium fluoride In tetrahydrofuran

4-methyl-2(5H)-furanone (6124-79-4) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
With Glycine max p51 reductase; NADPH In phosphate buffer at 36℃; for 12h; pH=7.0;

(3R)-4-(tert-butyl-diphenyl-silanyloxy)-3-methyl-thiobutyric acid S-methyl ester → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
With tetrabutyl ammonium fluoride

3-Methylbutenoic acid (541-47-9) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 45 percent / SeO2 2.1: H2; BINAP; chiral ruthenium catalyst 2.2: H(1+) View Scheme

MOM ether of (S)-(+)-methyl 3-hydroxy-2-methylpropionate (105164-20-3) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: 79 percent / LiAlH4 / diethyl ether / 4 h / Ambient temperature 2: 90 percent / pyridine / 0 - 5 °C 3: 90 percent / dimethylsulfoxide / 50 °C 4: 93 percent / aq. H2SO4 / aq. acetic acid / 1.5 h / Heating View Scheme

(R)-(+)-2-methyl-3-methoxymethyloxypropan-1-ol (126308-33-6) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 90 percent / pyridine / 0 - 5 °C 2: 90 percent / dimethylsulfoxide / 50 °C 3: 93 percent / aq. H2SO4 / aq. acetic acid / 1.5 h / Heating View Scheme

(S)-(+)-2-methyl-3-methoxymethyloxypropan-1-yl tosylate (222539-28-8) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 90 percent / dimethylsulfoxide / 50 °C 2: 93 percent / aq. H2SO4 / aq. acetic acid / 1.5 h / Heating View Scheme

(R)-(+)-3-methyldihydrofuran-2,5-dione (83247-83-0) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) calcium sulfate hemihydrate, 2.) molecular sieves 4 Angstroem / 1.) dioxane, 22 deg C, 45 h, lipozyme from Mucor miehei, 2.) cyclohexane, 22 deg C, 43 h, Novozym 435 from Candida antarctica 2: LiBH4 / tetrahydrofuran / 1 h / 50 °C View Scheme
Multi-step reaction with 2 steps 1: calcium sulfate hemihydrate / dioxane / 45 h / 22 °C / lipozyme from Mucor miehei 2: LiBH4 / tetrahydrofuran / 1 h / 50 °C View Scheme

(R)-3-(tetrahydro-2-pyranyloxy)-2-methyl-1-propanol (88728-99-8) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / pyridine 2: 70 percent / dimethylsulfoxide / 48 h / Ambient temperature 3: 46 percent / conc. HCl / methanol / 7 h / Heating View Scheme

(S)-3-(tetrahydro-2-pyranyloxy)-2-methylpropyl p-toluenesulfonate (88557-54-4, 96947-43-2) → (R)-3-methyl-γ-butyrolactone (65284-00-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 70 percent / dimethylsulfoxide / 48 h / Ambient temperature 2: 46 percent / conc. HCl / methanol / 7 h / Heating View Scheme

(R)-3-methyl-γ-butyrolactone (65284-00-6) → 4-bromo-3-methyl-butyric acid ethyl ester (56703-10-7)

Conditions	Yield
With hydrogen bromide In ethanol for 16h; Ambient temperature;	96%
With hydrogen bromide In ethanol

ethanol (64-17-5) + (R)-3-methyl-γ-butyrolactone (65284-00-6) → ethyl (R)-(+)-4-bromo-3-methylbutanoate (89363-48-4)

Conditions	Yield
With hydrogen bromide for 16h; Ambient temperature;	96%

Isobutyl iodide (513-38-2) + (R)-3-methyl-γ-butyrolactone (65284-00-6) → (2R)-2,6-dimethylheptan-1-ol (59983-44-7)

Conditions	Yield
Stage #1: Isobutyl iodide With tert.-butyl lithium In diethyl ether; pentane at -78 - 20℃; Stage #2: (R)-3-methyl-γ-butyrolactone In diethyl ether; pentane at -78℃; for 3h; Further stages;	79%

1-Iodooctane (629-27-6) + (R)-3-methyl-γ-butyrolactone (65284-00-6) → (R)-2-methyldodecan-1-ol (109034-03-9)

Conditions	Yield
Stage #1: 1-Iodooctane With tert.-butyl lithium In diethyl ether; pentane at -78 - 20℃; for 1.5h; Stage #2: (R)-3-methyl-γ-butyrolactone In diethyl ether; pentane at -78℃; for 3h; Further stages;	78%

(R)-3-methyl-γ-butyrolactone (65284-00-6) + 1-Iodohexane (638-45-9) → (R)-(+)-2-methyl-1-decanol (80698-14-2)

Conditions	Yield
Stage #1: 1-Iodohexane With tert.-butyl lithium In diethyl ether; pentane at -78 - 20℃; for 1.5h; Stage #2: (R)-3-methyl-γ-butyrolactone In diethyl ether; pentane at -78℃; for 3h; Further stages;	75%

(R)-3-methyl-γ-butyrolactone (65284-00-6) + prenyl bromide (870-63-3) → (2R,3R)-3-methyl-2-(3-methyl-2-butenyl)-4-butanolide (142746-33-6) + (2S,3R)-3-methyl-2-(3-methyl-2-butenyl)-4-butanolide (142795-62-8)

Conditions	Yield
With lithium diisopropyl amide 1) THF, -78 deg C, 1 h, 2) -78 deg C, 1 h; Yield given. Multistep reaction. Yields of byproduct given;

methyl cyanoformate (17640-15-2) + (R)-3-methyl-γ-butyrolactone (65284-00-6) → 3(R)-carbomethoxy-4(R)-methyldihydro-2(3H)-furanone (115047-73-9)

Conditions	Yield
With lithium diisopropyl amide 1.) THF, -78 deg C, 1.5 h, 2.) THF, -78 deg C, 3h; Yield given. Multistep reaction;

eschenmoser's salt (33797-51-2) + (R)-3-methyl-γ-butyrolactone (65284-00-6) → (R)-3-Dimethylaminomethyl-4-methyl-dihydro-furan-2-one

Conditions	Yield
With lithium diisopropyl amide 1.) THF, hexane, -78 deg C, 1 h, 2.) THF, hexane, a) -78 deg C, 1 h, b) RT, overnight; Multistep reaction;

(R)-3-methyl-γ-butyrolactone (65284-00-6) + (-)-(2E,4R)-5-methyl-2-hexen-4-ol (92283-72-2) → 4(R)-methyl-5(R)-(1(S),4-dimethyl-2(E)-pentenyl)dihydro-2(3H)furanone (106237-56-3)

Conditions	Yield
Multistep reaction;

(R)-3-methyl-γ-butyrolactone (65284-00-6) + (-)-(2E,4R)-5-methyl-2-hexen-4-ol (92283-72-2) → (3R,4S)-3-((E)-(S)-1,4-Dimethyl-pent-2-enyl)-4-methyl-dihydro-furan-2-one (106237-50-7, 106356-22-3, 106356-23-4, 106356-24-5, 110455-54-4, 110455-55-5, 115115-38-3, 122292-21-1) + 4(R)-methyl-3(R)-(1(S),4-dimethyl-2(E)-pentenyl)dihydro-2(3H)-furanone (110455-54-4) + 4(S)-methyl-3(S)-(1(S),4-dimethyl-2(E)-pentenyl)dihydro-2(3H)-furanone (106237-50-7) + 4(R)-methyl-3(S)-(1(S),4-dimethyl-2(E)-pentenyl)dihydro-2(3H)-furanone (110455-55-5)

Conditions	Yield
In toluene at 110℃; for 48h; Product distribution; Mechanism; investigation of the steric course Claisen rearrangements of lactone;
With acid In toluene at 110℃; for 48h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

(R)-3-methyl-γ-butyrolactone (65284-00-6) + trans-(R)-2-Octen-4-ol (84621-55-6) → (3R,4S)-4-Methyl-3-((E)-(S)-1-methyl-hept-2-enyl)-dihydro-furan-2-one (84564-83-0, 97277-06-0, 97277-07-1, 97277-08-2)

Conditions	Yield
With potassium tert-butylate; tert-butyl alcohol; Trimethylacetic acid 1) toluene, reflux, 2 d, 2) Et2O, 3 h, 25 degC; Yield given. Multistep reaction;

(R)-3-methyl-γ-butyrolactone (65284-00-6) + trans-(R)-2-Octen-4-ol (84621-55-6) → 4(R)-methyl-3(R)-(1(S)-methyl-2(E)-heptenyl)dihydro-2(3H)-furanone (97277-06-0) + 4(R)-methyl-3(S)-(1(S)-methyl-2(E)-heptenyl)dihydro-2(3H)-furanone (97277-07-1)

Conditions	Yield
Multistep reaction. Title compound not separated from byproducts;

(R)-3-methyl-γ-butyrolactone (65284-00-6) + trans-(R)-2-Octen-4-ol (84621-55-6) → 4(R)-methyl-3(S)-(1(S)-methyl-2(E)-heptenyl)dihydro-2(3H)-furanone (97277-07-1)

Conditions	Yield
Multistep reaction. Title compound not separated from byproducts;

Upstream product

• 108939-85-1 4,5-dimethylfuran-2-(3H)-one 
• 503-74-2 3-methylbutyric acid 
• 42856-49-5 (+/-)-1-benzyl-3-methyl-pyrrolidine-2,5-dione 
• 2938-98-9 2-methyl-1,4-butandiol 
• 1823-54-7 α-methyl-β-propiolactone 
• 201230-82-2 carbon monoxide 
• 96-48-0 4-butanolide 
• 125973-99-1 4-(Chloromethyl)-2(5H)-furanone 
• 82884-40-0 methyl 2-methyl-3-<(trimethylsilyl)oxy>-1-cyclopropanecarboxylate 
• 150-96-9 3-hydroxy-3-methylpentanoic acid 
• 7664-93-9 sulfuric acid 
• 41653-94-5 (Z)-3-Methyl-3-pentenoic Acid 
• 97-65-4 2-methylenesuccinic acid 
• 83247-83-0 (R)-(+)-3-methyldihydrofuran-2,5-dione 

Downstream Products

• 173310-48-0 2-methyl-4-oxo-5-(phenylthio)pentanol 
• 498-21-5 2-methylbutanedioic acid 
• 249613-77-2 2-(S)-3-(R,S)-2-azido-3-methyl-4-(phenylseleno)butanoic acid 
• 249613-79-4 2-(S)-3-(R,S)-methyl-2-[(tert-butoxycarbonyl)amino]-3-methyl-4-(phenylseleno)butanoate 
• 249613-78-3 2-(S)-3-(R,S)-2-[(tert-butoxycarbonyl)amino]-3-methyl-4-(phenylseleno)butanoic acid 
• 249613-75-0 3-(R,S)-4-(S)-benzyl-3-[3-methyl-4-(phenylseleno)butanoyl]-1,3-oxazolidin-2-one 
• 249613-76-1 2-(S)-3-(R,S)-4-(S)-3-[2-azido-3-methyl-4-(phenylseleno)butanoyl]-4-benzyl-1,3-oxazolidin-2-one 
• 249615-01-8 2-azido-3-[3-[2-(2-tert-butoxycarbonylamino-3-methyl-4-phenylselanyl-butyrylamino)-1-ethyl-3-methoxymethoxy-1-methyl-propoxy]-4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-3-(tert-butyl-dimethyl-silanyloxy)-propionic acid methyl ester 
• 503-74-2 3-methylbutyric acid 
• 74892-81-2 (2R-trans)-4-Methyl-2-piperidinecarboxylic acid 
• 249613-74-9 3-methyl-4-(phenylseleno)butanoic acid 
• 54145-05-0 4-methyl-3-phenylthio-4,5-dihydrofuran-2(3H)-one 
• 94807-92-8 (S)-3-methyl-4-phenylthiobutanoic acid 
• 888483-98-5 (R)-3-Methyl-4-phenylsulfanyl-butyric acid ethyl ester 

Relevant articles and documents

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A CONTRATHERMODYNAMIC EPIMERIZATION OF A 2,3-TRANS-DISUBSTITUTED BUTYROLACTONE: INTERMEDIATES FOR CHIRAL POLYPROPIONATE UNITS.

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Regioselective Hydrogenation of Itaconic Acid to Γ-Isovalerolactone by Transition-Metal Nanoparticle Catalysts

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METHODS OF FORMING DIOL COMPOUNDS

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