181289-33-8

Basic information

• Product Name: (R)-(-)-3-Carbamoymethyl-5-methylhexanoic acid
• Synonyms: (r)-(-)-3-(2-amino-2-oxoethyl)-5-methylhexanoic acid;(r)-(-)-3-carbamoymethyl-5-methylhexanoic acid;INTERMEDIATE OF PREGABALIN;(R)-3-(2-AMINO-2-OXOETHYL)-5-METHYLHEXANOIC ACID:99+%;3-CarbaMoyl Mehyl-5-Methyl Hexanoic Acid;(3R)-3-(2-AMino-2-oxoethyl)-5-Methylhexanoic Acid;Pregabalin IMpurity III;Hexanoic acid,3-(2-aMino-2-oxoethyl)-5-Methyl-,(3R)-
• CAS NO: 181289-33-8
• Molecular Formula: C₉H₁₇NO₃
• Molecular Weight: 187.23618
• EINECS: 1308068-626-2
• Product Categories: intermidiate of Pregablin;Starting Raw Materials & Intermediates;Aliphatics, Impurities, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 181289-33-8.mol

Chemical Properties

• Melting Point: 128-133°C
• Boiling Point: 401.929 °C at 760 mmHg
• Flash Point: 196.88 °C
• Appearance: /
• Density: 1.081 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.475
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 4.68±0.10(Predicted)
• CAS DataBase Reference: (R)-(-)-3-Carbamoymethyl-5-methylhexanoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-(-)-3-Carbamoymethyl-5-methylhexanoic acid(181289-33-8)
• EPA Substance Registry System: (R)-(-)-3-Carbamoymethyl-5-methylhexanoic acid(181289-33-8)

Safety Data

• Hazardous Substances Data: 181289-33-8(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 181289-33-8 differently. You can refer to the following data:
1. (R)-(-)-3-Carbamoymethyl-5-methylhexanoic acid is a useful chemical intermediate for manufacturing of the anticonvulsant drug, Pregabalin1, 2.
2. An Impurity of the anti-convulsant (S)-Pregabalin (P704790).

Sources

https://quod.lib.umich.edu/a/ark/5550190.0011.a22?rgn=main;view=fulltext https://www.researchgate.net/publication/269660675_Synthesis_and_characterization_of_impurities_of_an_anticonvulsant_drug_Pregabalin

Chemical Properties

White Solid

InChI:InChI=1/C9H17NO3/c1-6(2)3-7(4-8(10)11)5-9(12)13/h6-7H,3-5H2,1-2H3,(H2,10,11)(H,12,13)/t7-/m1/s1

Synthetic route

1‐phenylethan‐1‐amine 3‐(carbamoylmethyl)‐5‐methylhexanoate → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
Stage #1: 1‐phenylethan‐1‐amine 3‐(carbamoylmethyl)‐5‐methylhexanoate With hydrogenchloride In water at 10 - 30℃; for 2h; pH=0.5 - 2; Stage #2: With sulfuric acid In water at 6 - 40℃; for 3h; pH=1.5; Temperature; Reagent/catalyst; Solvent;	100%

3-isobutylglutarimide → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
With water In tetrahydrofuran at 45℃; for 15h; Reagent/catalyst; Solvent; Temperature;	96.1%

(3S)-3-(2-(allyloxy)-2-oxoethyl)-5-methylhexanoic acid (1403953-91-2) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
Stage #1: (3S)-3-(2-(allyloxy)-2-oxoethyl)-5-methylhexanoic acid With magnesium nitride In methanol at 20 - 80℃; for 16h; Stage #2: With hydrogenchloride In methanol; water pH=3 - 4;	93%

(±)‑3‑(carbamoylmethyl)‑5‑methylhexanoic acid (181289-15-6) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
With D-phenylglycine butyl ester In isopropyl alcohol Heating;	90.39%
With (R)-1-phenyl-ethyl-amine In methanol; chloroform at 25 - 40℃; for 3.16h; Solvent; Temperature;	41%
Stage #1: (±)‑3‑(carbamoylmethyl)‑5‑methylhexanoic acid With (R)-1-phenyl-ethyl-amine In ethanol; chloroform for 0.75h; Reflux; Stage #2: With hydrogenchloride In ethanol; chloroform; water for 0.75h; Cooling;	40%

(-)-3-cyclohexylsulfanylcarbonylmethyl-5-methyl-hexanoic acid (1237492-10-2) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
With ammonia In water at 40℃;	88%

(3S)-3-(2-ethoxy-2-oxoethyl)-5-methylhexanoic acid (1082077-07-3) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
Stage #1: (3S)-3-(2-ethoxy-2-oxoethyl)-5-methylhexanoic acid With ammonium iodide; sodium amide In tetrahydrofuran at 20℃; for 4h; Cooling with ice; Green chemistry; Stage #2: With hydrogenchloride In water pH=4 - 5; Reagent/catalyst; Solvent; Green chemistry;	86.7%
With ammonia; calcium chloride In methanol at 55 - 60℃; under 3000.3 - 3375.34 Torr; Autoclave;
With ammonia; calcium chloride In methanol at 25 - 70℃; under 375.038 - 2250.23 Torr; Autoclave;

(3S)-3-(2-methoxy-2-oxoethyl)-5-methylhexanoic acid (181289-25-8) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
Stage #1: (3S)-3-(2-methoxy-2-oxoethyl)-5-methylhexanoic acid With ammonia In water at 20 - 80℃; under 760.051 - 1520.1 Torr; for 6 - 92h; Stage #2: With hydrogenchloride In water pH=1 - 3; Product distribution / selectivity;	60%
Stage #1: (3S)-3-(2-methoxy-2-oxoethyl)-5-methylhexanoic acid With ammonia; ammonium chloride In water at 20 - 40℃; for 42.5h; Stage #2: With hydrogenchloride In water pH=4; Product distribution / selectivity;
Stage #1: (3S)-3-(2-methoxy-2-oxoethyl)-5-methylhexanoic acid With ammonia In water; toluene at 20℃; for 88h; Stage #2: With sulfuric acid In water pH=3; Product distribution / selectivity;
With ammonium hydroxide at 25 - 90℃; for 75h; Reagent/catalyst; Temperature;	75 g

(3R)-5-methyl-3-(2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)hexanoic acid (930585-94-7) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
Stage #1: (3R)-5-methyl-3-(2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)hexanoic acid With ammonia; water; lithium In tetrahydrofuran at -40℃; for 6 - 10h; Stage #2: With hydrogenchloride In water pH=1.5 - 1.7; Product distribution / selectivity;	59.37%
Stage #1: (3R)-5-methyl-3-(2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)hexanoic acid With ammonia; water; sodium In tetrahydrofuran at -40℃; for 6 - 10h; Stage #2: With hydrogenchloride In water pH=1.5 - 1.7; Product distribution / selectivity;	39.37%
With sulfuric acid In tetrahydrofuran at 25 - 30℃; Product distribution / selectivity;	39%
With palladium 10% on activated carbon; hydrogen In methanol at 30℃; under 7500.75 Torr; for 12h; Autoclave; Industrial scale;

R-(-)-3-(carbamoylmethyl)-5-methylhexanoic acid 1-phenylpropylamine salt (1385049-51-3) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
Stage #1: R-(-)-3-(carbamoylmethyl)-5-methylhexanoic acid 1-phenylpropylamine salt With ammonia In water at 80℃; for 5h; Stage #2: With hydrogenchloride In water at 0℃; pH=1;	53%

(R)-methyl 3-(carbamoylmethyl)-5-methylhexanoate → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
Stage #1: (R)-methyl 3-(carbamoylmethyl)-5-methylhexanoate With hydrogenchloride In water at 20 - 25℃; for 1 - 10h; Stage #2: With sodium hydroxide In water pH=3; Product distribution / selectivity;
Stage #1: (R)-methyl 3-(carbamoylmethyl)-5-methylhexanoate With hydrogenchloride; water at 20 - 25℃; Stage #2: With sodium hydroxide In water pH=3;

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;

(R)-(-)-phenylglycinol salt of (R)-(-)-3-(carbamoylmethyl)-5-methylhexanoic acid (1001296-65-6) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
With hydrogenchloride In water at 60 - 62℃;	n/a

(R)-3-(carbamoylmethyl)-5-methylhexanoic acid (R)-(+)-α-phenylethylamine (185815-61-6) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
With hydrogenchloride In water at 31℃; pH=1.7;
With hydrogenchloride In water at 20 - 25℃; for 1.47h;
With hydrogenchloride In water pH=1 - 2;	1.21 g

(±)‑3‑(carbamoylmethyl)‑5‑methylhexanoic acid (181289-15-6) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8) + (S)‑3‑carbamoylmethyl‑5‑methylhexanoic acid (181289-34-9)

Conditions	Yield
With (R)-1-phenyl-ethyl-amine Resolution of racemate;

(3S)-3-(2-methoxy-2-oxoethyl)-5-methylhexanoic acid (181289-25-8) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8) + (S)‑3‑carbamoylmethyl‑5‑methylhexanoic acid (181289-34-9)

Conditions	Yield
Stage #1: (3S)-3-(2-methoxy-2-oxoethyl)-5-methylhexanoic acid With ammonia In water at 20℃; for 92h; Stage #2: With hydrogenchloride In water pH=3;

5-methyl-3-carboxymethylhexanoic acid (75143-89-4) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: urea / 12 h / 130 - 135 °C 1.2: 60 - 90 °C 2.1: chloroform / 0.5 h / 50 - 55 °C 3.1: hydrogenchloride / water / 1.47 h / 20 - 25 °C View Scheme
Multi-step reaction with 4 steps 1.1: acetyl chloride / 3.08 h / 20 - 55 °C / Inert atmosphere 2.1: ammonia / water; tert-butyl methyl ether / 0 - 20 °C 2.2: pH 2 3.1: acetone / water / 80 °C 4.1: ammonia / water / 5 h / 80 °C 4.2: 0 °C / pH 1 View Scheme
Multi-step reaction with 4 steps 1.1: acetyl chloride / 3.08 h / 20 - 55 °C / Inert atmosphere 2.1: ammonia / water; tert-butyl methyl ether / 0 - 20 °C 2.2: pH 2 3.1: chloroform; ethanol / 0.75 h / 60 - 63 °C 4.1: ammonia / water / 5 h / 80 °C 4.2: 0 °C / pH 1 View Scheme

(S)‑3‑carbamoylmethyl‑5‑methylhexanoic acid (181289-34-9) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / Reflux 1.2: 25 - 65 °C 1.3: 1.5 h / 10 - 15 °C 2.1: chloroform / 0.5 h / 50 - 55 °C 3.1: hydrogenchloride / water / 1.47 h / 20 - 25 °C View Scheme

isovaleraldehyde (590-86-3) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: di-n-propylamine; ethyl 2-cyanoacetate / cyclohexane / 2 h / 25 - 30 °C / Reflux 1.2: 5.17 h / 25 - 50 °C 1.3: 48 h / Reflux 2.1: urea / 12 h / 130 - 135 °C 2.2: 60 - 90 °C 3.1: chloroform / 0.5 h / 50 - 55 °C 4.1: hydrogenchloride / water / 1.47 h / 20 - 25 °C View Scheme
Multi-step reaction with 7 steps 1.1: piperidine; pyridine; acetic acid / hexane / 48 h / Reflux; Inert atmosphere 2.1: di-n-propylamine / 16 h / 15 - 55 °C 3.1: hydrogen bromide / water / 72 h / 100 °C 4.1: acetyl chloride / 3.08 h / 20 - 55 °C / Inert atmosphere 5.1: ammonia / water; tert-butyl methyl ether / 0 - 20 °C 5.2: pH 2 6.1: acetone / water / 80 °C 7.1: ammonia / water / 5 h / 80 °C 7.2: 0 °C / pH 1 View Scheme
Multi-step reaction with 7 steps 1.1: piperidine; pyridine; acetic acid / hexane / 48 h / Reflux; Inert atmosphere 2.1: di-n-propylamine / 16 h / 15 - 55 °C 3.1: hydrogen bromide / water / 72 h / 100 °C 4.1: acetyl chloride / 3.08 h / 20 - 55 °C / Inert atmosphere 5.1: ammonia / water; tert-butyl methyl ether / 0 - 20 °C 5.2: pH 2 6.1: chloroform; ethanol / 0.75 h / 60 - 63 °C 7.1: ammonia / water / 5 h / 80 °C 7.2: 0 °C / pH 1 View Scheme

3-isobutylglutaric anhydride (185815-59-2) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: ammonia / water; tert-butyl methyl ether / 0 - 20 °C 1.2: pH 2 2.1: acetone / water / 80 °C 3.1: ammonia / water / 5 h / 80 °C 3.2: 0 °C / pH 1 View Scheme
Multi-step reaction with 3 steps 1.1: ammonia / water; tert-butyl methyl ether / 0 - 20 °C 1.2: pH 2 2.1: chloroform; ethanol / 0.75 h / 60 - 63 °C 3.1: ammonia / water / 5 h / 80 °C 3.2: 0 °C / pH 1 View Scheme
Multi-step reaction with 4 steps 1.1: 1,4-diaza-bicyclo[2.2.2]octane / tert-butyl methyl ether / 2 h / -78 °C / Inert atmosphere 2.1: chloroformic acid ethyl ester; triethylamine / acetone / -20 °C / Inert atmosphere 2.2: 2 h / -20 °C 2.3: 0 °C 3.1: acetone / water / 80 °C 4.1: ammonia / water / 5 h / 80 °C 4.2: 0 °C / pH 1 View Scheme
Multi-step reaction with 4 steps 1.1: 1,4-diaza-bicyclo[2.2.2]octane / tert-butyl methyl ether / 2 h / -78 °C / Inert atmosphere 2.1: chloroformic acid ethyl ester; triethylamine / acetone / -20 °C / Inert atmosphere 2.2: 2 h / -20 °C 2.3: 0 °C 3.1: chloroform; ethanol / 0.75 h / 60 - 63 °C 4.1: ammonia / water / 5 h / 80 °C 4.2: 0 °C / pH 1 View Scheme
Multi-step reaction with 2 steps 1: dmap / toluene / -20 - -10 °C / Industrial scale 2: hydrogen; palladium 10% on activated carbon / methanol / 12 h / 30 °C / 7500.75 Torr / Autoclave; Industrial scale View Scheme

diethyl 2-(3-methylbutylidene)malonate (51615-30-6) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: di-n-propylamine / 16 h / 15 - 55 °C 2.1: hydrogen bromide / water / 72 h / 100 °C 3.1: acetyl chloride / 3.08 h / 20 - 55 °C / Inert atmosphere 4.1: ammonia / water; tert-butyl methyl ether / 0 - 20 °C 4.2: pH 2 5.1: acetone / water / 80 °C 6.1: ammonia / water / 5 h / 80 °C 6.2: 0 °C / pH 1 View Scheme
Multi-step reaction with 6 steps 1.1: di-n-propylamine / 16 h / 15 - 55 °C 2.1: hydrogen bromide / water / 72 h / 100 °C 3.1: acetyl chloride / 3.08 h / 20 - 55 °C / Inert atmosphere 4.1: ammonia / water; tert-butyl methyl ether / 0 - 20 °C 4.2: pH 2 5.1: chloroform; ethanol / 0.75 h / 60 - 63 °C 6.1: ammonia / water / 5 h / 80 °C 6.2: 0 °C / pH 1 View Scheme
Multi-step reaction with 7 steps 1.1: di-n-propylamine / 16 h / 15 - 55 °C 2.1: hydrogen bromide / water / 72 h / 100 °C 3.1: acetyl chloride / 3.08 h / 20 - 55 °C / Inert atmosphere 4.1: 1,4-diaza-bicyclo[2.2.2]octane / tert-butyl methyl ether / 2 h / -78 °C / Inert atmosphere 5.1: chloroformic acid ethyl ester; triethylamine / acetone / -20 °C / Inert atmosphere 5.2: 2 h / -20 °C 5.3: 0 °C 6.1: chloroform; ethanol / 0.75 h / 60 - 63 °C 7.1: ammonia / water / 5 h / 80 °C 7.2: 0 °C / pH 1 View Scheme
Multi-step reaction with 7 steps 1.1: di-n-propylamine / 16 h / 15 - 55 °C 2.1: hydrogen bromide / water / 72 h / 100 °C 3.1: acetyl chloride / 3.08 h / 20 - 55 °C / Inert atmosphere 4.1: 1,4-diaza-bicyclo[2.2.2]octane / tert-butyl methyl ether / 2 h / -78 °C / Inert atmosphere 5.1: chloroformic acid ethyl ester; triethylamine / acetone / -20 °C / Inert atmosphere 5.2: 2 h / -20 °C 5.3: 0 °C 6.1: acetone / water / 80 °C 7.1: ammonia / water / 5 h / 80 °C 7.2: 0 °C / pH 1 View Scheme

2-isobutyl-propane-1,1,3,3-tetracarboxylic acid tetraethyl ester (102710-09-8) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: hydrogen bromide / water / 72 h / 100 °C 2.1: acetyl chloride / 3.08 h / 20 - 55 °C / Inert atmosphere 3.1: ammonia / water; tert-butyl methyl ether / 0 - 20 °C 3.2: pH 2 4.1: acetone / water / 80 °C 5.1: ammonia / water / 5 h / 80 °C 5.2: 0 °C / pH 1 View Scheme
Multi-step reaction with 5 steps 1.1: hydrogen bromide / water / 72 h / 100 °C 2.1: acetyl chloride / 3.08 h / 20 - 55 °C / Inert atmosphere 3.1: ammonia / water; tert-butyl methyl ether / 0 - 20 °C 3.2: pH 2 4.1: chloroform; ethanol / 0.75 h / 60 - 63 °C 5.1: ammonia / water / 5 h / 80 °C 5.2: 0 °C / pH 1 View Scheme
Multi-step reaction with 6 steps 1.1: hydrogen bromide / water / 72 h / 100 °C 2.1: acetyl chloride / 3.08 h / 20 - 55 °C / Inert atmosphere 3.1: 1,4-diaza-bicyclo[2.2.2]octane / tert-butyl methyl ether / 2 h / -78 °C / Inert atmosphere 4.1: chloroformic acid ethyl ester; triethylamine / acetone / -20 °C / Inert atmosphere 4.2: 2 h / -20 °C 4.3: 0 °C 5.1: chloroform; ethanol / 0.75 h / 60 - 63 °C 6.1: ammonia / water / 5 h / 80 °C 6.2: 0 °C / pH 1 View Scheme
Multi-step reaction with 6 steps 1.1: hydrogen bromide / water / 72 h / 100 °C 2.1: acetyl chloride / 3.08 h / 20 - 55 °C / Inert atmosphere 3.1: 1,4-diaza-bicyclo[2.2.2]octane / tert-butyl methyl ether / 2 h / -78 °C / Inert atmosphere 4.1: chloroformic acid ethyl ester; triethylamine / acetone / -20 °C / Inert atmosphere 4.2: 2 h / -20 °C 4.3: 0 °C 5.1: acetone / water / 80 °C 6.1: ammonia / water / 5 h / 80 °C 6.2: 0 °C / pH 1 View Scheme

(1'SR,3 SR)-1-(1'-napthyl)ethyl-3-(carboxylomethyl)-5-methylhexanoate (1385049-46-6) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: chloroformic acid ethyl ester; triethylamine / acetone / -20 °C / Inert atmosphere 1.2: 2 h / -20 °C 1.3: 0 °C 2.1: acetone / water / 80 °C 3.1: ammonia / water / 5 h / 80 °C 3.2: 0 °C / pH 1 View Scheme
Multi-step reaction with 3 steps 1.1: chloroformic acid ethyl ester; triethylamine / acetone / -20 °C / Inert atmosphere 1.2: 2 h / -20 °C 1.3: 0 °C 2.1: chloroform; ethanol / 0.75 h / 60 - 63 °C 3.1: ammonia / water / 5 h / 80 °C 3.2: 0 °C / pH 1 View Scheme

R-(-)-3-(carbamoylmethyl)-5-methylhexanoic acid quinine salt → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
Stage #1: R-(-)-3-(carbamoylmethyl)-5-methylhexanoic acid quinine salt With ammonia In water at 80℃; for 5h; Stage #2: With hydrogenchloride In water at 0℃; pH=1;

1,5-diallyl 3-isobutylpentanedioate (1403953-90-1) → (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid (181289-33-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: immobilized lipase B from Candida antartica; sodium hydroxide / aq. phosphate buffer / 15.6 h / 25 °C / pH 7 / Enzymatic reaction 2.1: magnesium nitride / methanol / 16 h / 20 - 80 °C 2.2: pH 3 - 4 View Scheme

Upstream product

• 181289-25-8 (3S)-3-(2-methoxy-2-oxoethyl)-5-methylhexanoic acid 
• 67-56-1 methanol 
• 185815-59-2 3-isobutylglutaric anhydride 
• 1001296-65-6 (R)-(-)-phenylglycinol salt of (R)-(-)-3-(carbamoylmethyl)-5-methylhexanoic acid 
• 930585-94-7 (3R)-5-methyl-3-(2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)hexanoic acid 
• 185815-61-6 (R)-3-(carbamoylmethyl)-5-methylhexanoic acid (R)-(+)-α-phenylethylamine 
• 181289-15-6 (±)?3?(carbamoylmethyl)?5?methylhexanoic acid 
• 1237492-10-2 (-)-3-cyclohexylsulfanylcarbonylmethyl-5-methyl-hexanoic acid 
• 75143-89-4 5-methyl-3-carboxymethylhexanoic acid 
• 181289-34-9 (S)?3?carbamoylmethyl?5?methylhexanoic acid 
• 590-86-3 isovaleraldehyde 
• 51615-30-6 diethyl 2-(3-methylbutylidene)malonate 
• 102710-09-8 2-isobutyl-propane-1,1,3,3-tetracarboxylic acid tetraethyl ester 
• 1385049-46-6 (1'SR,3 SR)-1-(1'-napthyl)ethyl-3-(carboxylomethyl)-5-methylhexanoate 

Downstream Products

• 148553-50-8 pregabilin 
• 128013-69-4 (R,S)-3-iso-butyl-4-aminobutyric acid 
• 1136478-30-2 3-(aminomethyl)-5-methylhex-5-enoic acid 
• 216576-74-8 3-(aminomethyl)-5-methylhex-4-enoic acid 
• 1237492-12-4 C₁₅H₂₀N₂O₅ 
• 75143-89-4 5-methyl-3-carboxymethylhexanoic acid 
• 61312-87-6 4-(2-methylpropyl)pyrrolidin-2-one 
• 181289-23-6 (S)-4-isobutyl-pyrrolidin-2-one 

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In the present study, we aimed to optimize the synthesis stages of S-pregabalin ((S)-3-(aminomethyl)-5-methylhexanoic acid), a well-known anticonvulsant drug. We used appropriate solvents and compounds to reach a straightforward and applicable method. The advantages of this research were avoiding use of expensive and environment pollutant reagents and solvents, and also using a recoverable reagent. Discarding prevention of the intermediates and reagents besides attaining a higher yield of the obtained product were the additional achievements. All structures were characterized by FT-IR, 1H NMR, and the purity of S-pregabalin was evaluated using the HPLC assay.

Method for synthesizing optically pure (R)-3-carbamoymethyl-5-methylhexanoic acid

The invention relates to the technical field of fine chemical engineering production and in particular discloses a method for synthesizing optically pure (R)-3-carbamoymethyl-5-methylhexanoic acid. The method comprises the following steps: 1, synthesizing 2-cyano-5-methyl-2-ene ethyl hexanoate; 2, synthesizing 3-isobutyl-2-cyano-4-ethoxycarbonyl-ethyl glutarate; 3, synthesizing 3-isobutylglutaricanhydride; 4, synthesizing (+/-)-3-carbamoymethyl-5-methylhexanoic acid; and 5, synthesizing the (R)-3-carbamoymethyl-5-methylhexanoic acid. According to the method disclosed by the invention, the defects in the prior art are overcome, and the provided synthetic method is low in raw material cost, high in reaction speed, simple and feasible, is suitable for large-scale industrial production and has very high economic benefits.

Preparation method of pregabalin intermediate (R)-3-carbamoyl methyl-5-methylhexanoic acid

The invention relates to a preparation method of key intermediate (R)-3-carbamoyl methyl-5-methylhexanoic acid of pregabalin treating epilepsy, neuropathic pain and anxiety. The method uses cyanoacetamide and isovaleraldehyde as starting materials to prepare 3-isobutylglutaric acid, 3-isobutylglutaric acid is esterified, enzymatically reacted and aminolyzed to produce the pregabalin intermediate (R)-3-carbamoyl methyl-5-methylhexanoic acid. The invention has the advantages of low cost, simple reaction, environmental friendliness and high yield, and is suitable for industrial production.

AN IMPROVED PROCESS FOR THE PREPARATION OF PREGABALIN

The present invention relates to an improved process for the preparation of 3-isobutyl glutaric acid compound of formula-1 which is used as the key intermediate in the preparation of Pregabalin compound of formula-A. The present invention also relates to an improved process for the preparation of (S)-3-(aminomethyl)-5-methylhexanoic acid compound of formula-A.

Method for synthesizing pregabalin midbody

The invention discloses a method for synthesizing a pregabalin midbody, and belongs to the technical field of medicine preparation. According to the method for synthesizing the pregabalin midbody, ammonium chloride, ammonium bicarbonate, ammonium carbonate, ammonium oxalate, ammonium formate, ammonium bromide, ammonium iodide, ammonium hydroxide, formamide, acetamide, hydrazine hydrate and other solid or liquid substances are used as an ammonia source, under the action of alkaline, (S)-3-(ethoxy-formyl methyl)-5-methyl caproic acid is subjected to a room temperature reaction, and pregabalin midbody (R)-3-(carbamyl methyl)-5-methyl caproic acid is generated. The method for synthesizing the pregabalin midbody is simple to operate, the pregabalin midbody can be obtained with high yield underordinary-pressure room temperature, the reaction condition is mild, economic and environmentally friendly, and the method for synthesizing the pregabalin midbody is suitable for industrial production.

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.

IMPROVED PROCESS FOR THE PREPARATION OF PREGABALIN

Disclosed is the process suitable for industrial synthesis of Pregabalin from (R)-(-)-3- (carbamoylmethyl)-5-methylhexanoic using sodium hypochlorite with low ash content by means of reverse addition.