185815-59-2

Basic information

• Product Name: 3-isobutylglutaric anhydride
• Synonyms: 3-isobutylglutaric anhydride;Dihydro-4-(2-methylpropyl)-2H-pyran-2,6(3H)-dione;4-isobutyl-dihydro-3H-pyran-2,6-dione;4-Isobutyldihydro-2H-pyran-2,6(3H)-dione;2H-Pyran-2,6(3H)-dione,dihydro-4-(2-Methylpropyl)-
• CAS NO: 185815-59-2
• Molecular Formula: C₉H₁₄O₃
• Molecular Weight: 170.21
• Mol File: 185815-59-2.mol
• Article Data: 15

Chemical Properties

• Boiling Point: 279.3 °C at 760 mmHg
• Flash Point: 124 °C
• Appearance: /
• Density: 1.054
• Vapor Pressure: 0.00406mmHg at 25°C
• Refractive Index: 1.451
• CAS DataBase Reference: 3-isobutylglutaric anhydride(CAS DataBase Reference)
• NIST Chemistry Reference: 3-isobutylglutaric anhydride(185815-59-2)
• EPA Substance Registry System: 3-isobutylglutaric anhydride(185815-59-2)

Safety Data

• Hazardous Substances Data: 185815-59-2(Hazardous Substances Data)

Usage

Uses

3-Isobutylglutaric anhydride is an impurity of Pregabalin (P704800), a ligand for the alpha-2-delta subunit of voltage-gated calcium channels that exhibits anticonvulsant and analgesic activity.

InChI:InChI=1/C9H14O3/c1-6(2)3-7-4-8(10)12-9(11)5-7/h6-7H,3-5H2,1-2H3

Synthetic route

5-methyl-3-carboxymethylhexanoic acid (75143-89-4) → 3-isobutylglutaric anhydride (185815-59-2)

Conditions	Yield
With propionic acid anhydride at 140 - 145℃; for 6h;	91%
With acetyl chloride at 20 - 55℃; for 3.08333h; Inert atmosphere;	85%
at 150℃; unter vermindertem Druck;

isovaleraldehyde (590-86-3) + cyanoacetic acid amide (107-91-5) → 3-isobutylglutaric anhydride (185815-59-2)

Conditions	Yield
Stage #1: isovaleraldehyde; cyanoacetic acid amide; piperidine In dichloromethane; water at 22 - 25℃; for 6h; Stage #2: With hydrogenchloride In water for 20h; Heating; Stage #3: With acetic anhydride for 2h; Heating; Further stages.;	65%

diethyl 2-(3-methylbutylidene)malonate (51615-30-6) → 3-isobutylglutaric anhydride (185815-59-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: di-n-propylamine / 16 h / 15 - 55 °C 2: hydrogen bromide / water / 72 h / 100 °C 3: acetyl chloride / 3.08 h / 20 - 55 °C / Inert atmosphere View Scheme

2-isobutyl-propane-1,1,3,3-tetracarboxylic acid tetraethyl ester (102710-09-8) → 3-isobutylglutaric anhydride (185815-59-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen bromide / water / 72 h / 100 °C 2: acetyl chloride / 3.08 h / 20 - 55 °C / Inert atmosphere View Scheme

isovaleraldehyde (590-86-3) → 3-isobutylglutaric anhydride (185815-59-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: piperidine; pyridine; acetic acid / hexane / 48 h / Reflux; Inert atmosphere 2: di-n-propylamine / 16 h / 15 - 55 °C 3: hydrogen bromide / water / 72 h / 100 °C 4: acetyl chloride / 3.08 h / 20 - 55 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: tetramethyl ammoniumhydroxide; trimethyldodecylammonium chloride / ethanol / 6 h / 25 °C 2: water; hydrogenchloride / 30 h / 140 °C / pH 1 - 2 3: acetic anhydride / 2 h / 120 °C View Scheme

2,4-dicyano-3-isobutylglutaramide → 3-isobutylglutaric anhydride (185815-59-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: water; hydrogenchloride / 30 h / 140 °C / pH 1 - 2 2: acetic anhydride / 2 h / 120 °C View Scheme

3-isobutylglutaric anhydride (185815-59-2) → (±)‑3‑(carbamoylmethyl)‑5‑methylhexanoic acid (181289-15-6)

Conditions	Yield
With ammonia In water at -10 - 40℃; for 1.5h;	100%
With ammonium hydroxide at 10℃; for 2h; Temperature;	95%
Stage #1: 3-isobutylglutaric anhydride With ammonia In tert-butyl methyl ether; water at 0 - 20℃; Stage #2: With hydrogenchloride In tert-butyl methyl ether; water pH=2;	80.4%

3-isobutylglutaric anhydride (185815-59-2) + Cyclohexanethiol (1569-69-3) → (-)-3-cyclohexylsulfanylcarbonylmethyl-5-methyl-hexanoic acid (1237492-10-2)

Conditions	Yield
In tert-butyl methyl ether at 20℃; for 72h; Product distribution / selectivity; Inert atmosphere;	100%

3-isobutylglutaric anhydride (185815-59-2) + (R)-1-phenyl-ethyl-amine (3886-69-9) → (3R)-5-methyl-3-(2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)hexanoic acid (930585-94-7)

Conditions	Yield
Stage #1: 3-isobutylglutaric anhydride; (R)-1-phenyl-ethyl-amine With dmap In ethyl acetate at 0 - 5℃; for 1.75 - 2.33h; Stage #2: With sodium hydrogencarbonate In water; ethyl acetate Stage #3: With hydrogenchloride In water pH=2 - 2.5; Product distribution / selectivity;	99.3%
Stage #1: 3-isobutylglutaric anhydride; (R)-1-phenyl-ethyl-amine With dmap In isopropyl alcohol at 0 - 5℃; for 1.75 - 2.33h; Stage #2: With sodium hydrogencarbonate In water; isopropyl alcohol Stage #3: With hydrogenchloride In water pH=2 - 2.5; Product distribution / selectivity;	99.34%
Stage #1: 3-isobutylglutaric anhydride; (R)-1-phenyl-ethyl-amine With dmap In toluene at 0 - 5℃; for 1.75 - 2.33h; Stage #2: With sodium hydrogencarbonate In water; toluene Stage #3: With hydrogenchloride In water pH=2 - 2.5; Product distribution / selectivity;	99.6%

methanol (67-56-1) + 3-isobutylglutaric anhydride (185815-59-2) → 3-isobutylglutaric acid methyl ester (181289-11-2)

Conditions	Yield
at 20℃; for 16 - 18h; Product distribution / selectivity;	97%
Stage #1: methanol; 3-isobutylglutaric anhydride With triethylamine at 20℃; for 16 - 18h; Stage #2: With hydrogenchloride; water Product distribution / selectivity;	95%

methanol (67-56-1) + 3-isobutylglutaric anhydride (185815-59-2) → (3R)-3-(2-methoxy-2-oxoethyl)-5-methylhexanoic acid (156048-92-9)

Conditions	Yield
With N-((1S)-(6-methoxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)-3,5-bis(trifluoromethyl)benzenesulfonamide In tert-butyl methyl ether at -20℃; for 14h; optical yield given as %ee; enantioselective reaction;	96%
Stage #1: methanol; 3-isobutylglutaric anhydride; Q-BTBSA In tert-butyl methyl ether at -20℃; for 14h; Stage #2: With hydrogenchloride In tert-butyl methyl ether; water Product distribution / selectivity;	96%
With Quinine In toluene at -70℃; for 17h; Product distribution / selectivity;	95%
With Cinchonidin In toluene at -50℃; for 15h; Product distribution / selectivity;

3-isobutylglutaric anhydride (185815-59-2) + phenylmethanethiol (100-53-8) → (R)-3-(2-(benzylthio)-2-oxoethyl)-5-methylhexanoic acid (1432752-42-5)

Conditions	Yield
With N-((1R,2R)-2-(dimethylamino)-1-(4-nitrophenyl)-3-(trityloxy)propyl)-3,5-bis(trifluoromethyl)benzene-sulfonamide In tert-butyl methyl ether at -20℃; Inert atmosphere; Schlenk technique; enantioselective reaction;	96%

3-isobutylglutaric anhydride (185815-59-2) + phenylmethanethiol (100-53-8) → C16H22O3S

Conditions	Yield
With (S)-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)-N,N,4-trimethyl-N-(4-nitrobenzyl)(pentan-1-ylammonium) chloride In tert-butyl methyl ether at -10℃; for 16h; Solvent; Reagent/catalyst; Inert atmosphere;	96%

methanol (67-56-1) + 3-isobutylglutaric anhydride (185815-59-2) → (3S)-3-(2-methoxy-2-oxoethyl)-5-methylhexanoic acid (181289-25-8)

Conditions	Yield
With Cinchonin In toluene at -78 - -50℃; for 15 - 19h; Product distribution / selectivity;	90%
With quinidine In toluene at -78 - -50℃; for 2 - 96h; Product distribution / selectivity;	87%
In tert-butyl methyl ether at 20 - 25℃; for 3h; Enzymatic reaction;	n/a

3-isobutylglutaric anhydride (185815-59-2) + isopropyl alcohol (67-63-0) → isopropyl {4-methyl-2-[(1-carboxy)-methyl]-pentyl}-carbamate (1082077-22-2)

Conditions	Yield
Stage #1: isopropyl alcohol With sodium azide; zinc(II) chloride at 20℃; Inert atmosphere; Stage #2: 3-isobutylglutaric anhydride at 75 - 80℃; Stage #3: With hydrogenchloride; sodium nitrite In water at -5 - 10℃;	90%

3-isobutylglutaric anhydride (185815-59-2) → 1-hydroxy-4-(2-methylpropyl)piperidine-2,6-dione

Conditions	Yield
With hydroxylamine hydrochloride; sodium hydroxide In water; isopropyl alcohol at 60 - 65℃; for 4h;	90%

3-isobutylglutaric anhydride (185815-59-2) → 3-hydrazinocarbonylmethyl-5-methyl-hexanoic acid (1159446-16-8)

Conditions	Yield
With sodium hydroxide; hydrazine In water; toluene at -5 - 5℃; for 2 - 3h; Product distribution / selectivity;	86%
With sodium hydroxide; hydrazine In water; toluene at -5 - 5℃; for 2 - 3h; Product distribution / selectivity;	86%
With sodium hydroxide; hydrazine In water at -5 - 5℃; for 2 - 3h; Product distribution / selectivity;
With sodium hydroxide; hydrazine In water at -5 - 5℃; for 2 - 3h; Product distribution / selectivity;

3-isobutylglutaric anhydride (185815-59-2) + 4-Bromobutyl acetate (4753-59-7) → C14H26O4

Conditions	Yield
With [2,2]bipyridinyl; bis(1,5-cyclooctadiene)nickel (0); zinc In N,N-dimethyl acetamide at 80℃; for 12h;	83%

3-isobutylglutaric anhydride (185815-59-2) + 1-bromo-6-benzyloxyhexane (54247-27-7) → C21H34O3

Conditions	Yield
With [2,2]bipyridinyl; bis(1,5-cyclooctadiene)nickel (0); zinc In N,N-dimethyl acetamide at 80℃; for 12h;	80%

3-isobutylglutaric anhydride (185815-59-2) + (S)-1-phenyl-ethylamine (2627-86-3) → (3S)-5-methyl-3-(2-oxo-2-{[(1S)-1-phenylethyl]amino}ethyl)hexanoic acid (930280-42-5)

Conditions	Yield
With dmap In toluene at -15 - -10℃; Temperature; Concentration;	73%

3-isobutylglutaric anhydride (185815-59-2) + (2E)-3-phenyl-2-propen-1-ol (4407-36-7) → (-)-(R)-3-isobutyl-pentanedioic acid mono-(3-phenyl-allyl) ester (949890-69-1)

Conditions	Yield
With Quinine In toluene at -30℃; for 24h;	72%

3-isobutylglutaric anhydride (185815-59-2) + 3-Phenylpropenol (104-54-1) → (-)-(R)-3-isobutyl-pentanedioic acid mono-(3-phenyl-allyl) ester (949890-69-1)

Conditions	Yield
Stage #1: 3-isobutylglutaric anhydride; 3-Phenylpropenol With quinine In toluene at -35℃; for 24.25h; Stage #2: With 1-Adamantanamine In tert-butyl methyl ether; isopropyl alcohol at 25 - 45℃; for 6h; Stage #3: With hydrogenchloride In water; toluene Product distribution / selectivity;	69%
Stage #1: 3-isobutylglutaric anhydride; 3-Phenylpropenol With quinindine In di-isopropyl ether; water; toluene at -35℃; for 24.25h; Stage #2: With (S)-1-phenyl-ethylamine In di-isopropyl ether; water at 25 - 35℃; for 4h; Stage #3: With hydrogenchloride In water; toluene Product distribution / selectivity;	66%

3-isobutylglutaric anhydride (185815-59-2) + 3-Phenylpropenol (104-54-1) → (S)-3-(2-(cinnamyloxy)-2-oxoethyl)-5-methylhexanoic acid

Conditions	Yield
Stage #1: 3-isobutylglutaric anhydride; 3-Phenylpropenol With quinindine In toluene at -38 - -35℃; for 24.25h; Stage #2: With (S)-1-phenyl-ethylamine In di-isopropyl ether; water at 25 - 35℃; for 4h; Stage #3: With hydrogenchloride In water; toluene	65%

3-isobutylglutaric anhydride (185815-59-2) + aniline (62-53-3) → 3-isobutyl-N-phenyl-glutaramic acid

3-isobutylglutaric anhydride (185815-59-2) + phenylmagnesium chloride (100-59-4) → (R)-5-Methyl-3-(2-oxo-2-phenyl-ethyl)-hexanoic acid + (S)-5-Methyl-3-(2-oxo-2-phenyl-ethyl)-hexanoic acid

Conditions	Yield
With (-)-sparteine In toluene at -78℃; for 24h; Grignard reaction; Title compound not separated from byproducts;

3-isobutylglutaric anhydride (185815-59-2) → (S)-3-{[(2S-1,3,3,trimethylbicyclo[2.2.1]heptan-2-yloxy)carbonyl]methyl}-5-methylhexanoic aic (1057113-79-7) + (R)-3-{[(2S-1,3,3,trimethylbicyclo[2.2.1]heptan-2-yloxy)carbonyl]methyl}-5-methylhexanoic aic (1057113-81-1)

Conditions	Yield
Stage #1: (1S)-1,3,3-trimethyl-norbornan-2endo-ol With sodium hydride In toluene at 80℃; Stage #2: 3-isobutylglutaric anhydride In toluene at 0 - 20℃; for 3h;

3-isobutylglutaric anhydride (185815-59-2) → (S)-4-(((S)-carboxy(phenyl)methoxy)carbonyl)-3-isobutylbutanoic acid (959624-21-6) + (R)-4-(((S)-carboxy(phenyl)methoxy)carbonyl)-3-isobutylbutanoic acid (1057113-78-6)

Conditions	Yield
Stage #1: (S)-Mandelic acid With sodium hydride In toluene Heating / reflux; Stage #2: 3-isobutylglutaric anhydride In toluene at 20℃; for 6h;

methanol (67-56-1) + 3-isobutylglutaric anhydride (185815-59-2) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
Stage #1: methanol; 3-isobutylglutaric anhydride With quinidine at -50℃; for 17h; Stage #2: With ammonia In water at 20 - 40℃; for 72h; Stage #3: With hydrogenchloride In water pH=3; Product distribution / selectivity;

3-isobutylglutaric anhydride (185815-59-2) + benzyl alcohol (100-51-6) → (S)-3-isobutyl-pentanedioic acid monobenzyl ester + (R)-3-isobutyl-pentanedioic acid monobenzyl ester

Conditions	Yield
With Quinine In toluene at -25℃; for 23h; Title compound not separated from byproducts.;
With quinine In toluene at 20℃; for 20h; optical yield given as %ee; enantioselective reaction;
With xanthene-9-carboxylic acid; quinine In toluene at 20℃; for 20h; optical yield given as %ee; enantioselective reaction;
With xanthene-9-carboxylic acid; quinindine In toluene at 20℃; for 22h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;
With xanthene-9-carboxylic acid; quinine In toluene at 20℃; for 18h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;

3-isobutylglutaric anhydride (185815-59-2) → (-)-(S)-5-methyl-3-[(3-phenyl-allyloxycarbonylamino)methyl]-hexanoic acid 3-phenyl-allyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 72 percent / quinine / toluene / 24 h / -30 °C 2.1: triethylamine; diphenylphosphoryl azide / toluene / 20 - 90 °C 2.2: toluene / Heating View Scheme

3-isobutylglutaric anhydride (185815-59-2) → (-)-(S)-3-(benzyloxycarbonylamino-methyl)-5-methyl-hexanoic acid 3-phenyl-allyl ester (949890-73-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 72 percent / quinine / toluene / 24 h / -30 °C 2.1: triethylamine; diphenylphosphoryl azide / toluene / 20 - 90 °C 2.2: toluene / Heating View Scheme

3-isobutylglutaric anhydride (185815-59-2) → (-)-(S)-3-(benzyloxycarbonylamino-methyl)-5-methyl-hexanoic acid (949890-75-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 72 percent / quinine / toluene / 24 h / -30 °C 2.1: triethylamine; diphenylphosphoryl azide / toluene / 20 - 90 °C 2.2: toluene / Heating 3.1: 12.7 g / morpholine; triphenylphosphine / Pd(OAc)2 / ethanol / 3 h / Heating View Scheme
Multi-step reaction with 4 steps 1.1: N-((1R,2R)-2-(dimethylamino)-1-(4-nitrophenyl)-3-(trityloxy)propyl)-3,5-bis(trifluoromethyl)benzene-sulfonamide / tert-butyl methyl ether / -20 °C / Inert atmosphere; Schlenk technique 2.1: triethylamine; diphenyl phosphoryl azide / toluene / 20 - 90 °C / Inert atmosphere; Schlenk technique 3.1: toluene / Reflux; Inert atmosphere; Schlenk technique 4.1: lithium hydroxide; dihydrogen peroxide / water; tetrahydrofuran / 3 h / 20 °C / Inert atmosphere; Schlenk technique 4.2: 0 °C / Inert atmosphere; Schlenk technique View Scheme
Multi-step reaction with 3 steps 1.1: (S)-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)-N,N,4-trimethyl-N-(4-nitrobenzyl)(pentan-1-ylammonium) chloride / tert-butyl methyl ether / 16 h / -10 °C / Inert atmosphere 2.1: triethylamine; diphenylphosphoranyl azide / toluene / 0.25 h / 25 - 85 °C 2.2: 12 h / Reflux 3.1: lithium hydroxide; dihydrogen peroxide / tetrahydrofuran / 4 h / 20 °C View Scheme

3-isobutylglutaric anhydride (185815-59-2) → (S)-4-isobutyl-pyrrolidin-2-one (181289-23-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 72 percent / quinine / toluene / 24 h / -30 °C 2.1: triethylamine; diphenylphosphoryl azide / toluene / 20 - 90 °C 2.2: toluene / Heating 3.1: morpholine; triphenylphosphine / Pd(OAc)2 / ethanol / 3 h / Heating View Scheme

Upstream product

• 185815-56-9 2,4-dicyano-3-isobutylglutaramide 
• 590-86-3 isovaleraldehyde 
• 102710-09-8 2-isobutyl-propane-1,1,3,3-tetracarboxylic acid tetraethyl ester 
• 51615-30-6 diethyl 2-(3-methylbutylidene)malonate 
• 107-91-5 cyanoacetic acid amide 
• 75143-89-4 5-methyl-3-carboxymethylhexanoic acid 

Downstream Products

• 949890-69-1 (-)-(R)-3-isobutyl-pentanedioic acid mono-(3-phenyl-allyl) ester 
• 181289-25-8 (3S)-3-(2-methoxy-2-oxoethyl)-5-methylhexanoic acid 
• 156048-92-9 (3R)-3-(2-methoxy-2-oxoethyl)-5-methylhexanoic acid 
• 128013-69-4 (R,S)-3-iso-butyl-4-aminobutyric acid 
• 181289-33-8 (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid 
• 1385049-51-3 R-(-)-3-(carbamoylmethyl)-5-methylhexanoic acid 1-phenylpropylamine salt 
• 930280-44-7 {(S)-4-methyl-2-[((S)-1-phenylethylcarbamoyl)methyl]pentyl}carbamic acid methyl ester 
• 930280-42-5 (3S)-5-methyl-3-(2-oxo-2-{[(1S)-1-phenylethyl]amino}ethyl)hexanoic acid 
• 1231239-92-1 C₂₀H₃₀O₃S 
• 1231240-08-6 (R)-1-(2,4,6-trimethyl-phenyl)-ethanethiol 
• 1001651-79-1 C₁₈H₂₄O₄ 
• 181289-15-6 (±)?3?(carbamoylmethyl)?5?methylhexanoic acid 
• 930585-94-7 (3R)-5-methyl-3-(2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)hexanoic acid 
• 148553-50-8 pregabilin 

Relevant articles and documents

Pregabalin intermittent synthesis method

The invention discloses a pregabalin intermittent synthesis method. The method comprises the following step of (1) preparation of 2-cyano-5-methyl-2-hexenyl ethyl ester (A), wherein 94.6 g (1.1mol) ofisovaleraldehyde, 113 g (1.0 mol) of ethyl cyanoacetate, 127 ml of n-hexane and 1.00 g (0.01mol) of di-n-propylamine are put into a 1000 ml reaction bottle in sequence, heating is conducted, reflux reaction is carried out, a water separator is used for water separation, the reaction is carried out until no moisture is separated out, and cooling is conducted. Compared with the prior art, the pregabalin intermittent synthesis method has the following advantages that when methyl tertiary butyl ether is used as a solvent, layering is hard, impurities cannot be removed, the solvent cannot be recycled, the raw material cost is improved, and the amide is low, so that the methyl tertiary butyl ether is not suitable for being used as the solvent; ethyl acetate can be used, however, the intersolubility of the ethyl acetate and water is large, thus a small amount of amide crude product is dissolved in the water, the amide yield is low, meanwhile, the ethyl acetate recovery is low, and by using methylbenzene, the defects of the ethyl acetate are avoided, so that the methylbenzene is selected as an ammoniation solvent. There are no corresponding HPLC standards of the quality situation of amide, however, the quality of the amide obtained by adopting a technology is qualified in later detection.

Asymmetrical synthesis method of lyrica

The invention discloses an asymmetrical synthesis method of lyrica, wherein the synthesis steps comprise: carrying out a cyclic anhydridization reaction by using 3-isobutylglutaric acid as a raw material, carrying out an asymmetric ring-opening reaction with (R)-(+)-1-phenylethylamine, and sequentially carrying out a hydrogenation reaction and Huffman rearrangement to obtain lyrica. Compared to the synthesis method in the prior art, the synthesis method of the present invention has advantages of inexpensive and easily-available raw materials and less reaction steps, has the total yield of up to 60%, the purity of the product lyrica of more than 99% and the ee value of more than 99%, and has good application prospect in industrial scale up production.

Preparation method for 3-carbamoymethyl-5-methylhexanoic acid

The invention relates to a preparation method for 3-carbamoymethyl-5-methylhexanoic acid, and the product can be used as a pregabalin intermediate. The preparation method comprises the steps that a condensation compound is generated by catalytic condensation using isovaleraldehyde and cyanoacetamide as raw materials under mild conditions; the condensation compound is hydrolyzed to generate 3-Isobutylglutaric acid under acidic conditions; 3-isobutylglutaric anhydride is generated through an anhydride reaction; the final product 3-carbamoymethyl-5-methylhexanoic acid is generated through an amidation reaction. The preparation method for 3-carbamoymethyl-5-methylhexanoic acid effectively improves the condensation reaction efficiency through catalytic condensation of a base catalyst, and is high in production yield, less in by-products, mild in reaction conditions, and is beneficial to treatment of three wastes, and provides an environment-friendly technological route for industrialized mass production. The preparation method is an operation-safety, high-yield, low-cost and environment-friendly route.