55-40-3

Basic information

• Product Name: 2-METHYL-3-(3,4-DIHYDROXYPHENYL)-DL-ALANINE
• Synonyms: TIMTEC-BB SBB000508;DL-ALPHA-METHYL-DOPA;DL-METHYLDOPA;ALPHA-METHYL-DL-BETA-3,4-DIHYDROXYPHENYLALANINE;3-(3,4-DIHYDROXYPHENYL)-2-METHYL ALANINE;(+/-)-3-(3,4-DIHYDROXYPHENYL)-2-METHYL-DL-ALANINE;3-hydroxy-alpha-methyltyrosine;DL-Methyldopa sesquihydrate
• CAS NO: 55-40-3
• Molecular Formula: C₁₀H₁₃NO₄
• Molecular Weight: 211.21
• EINECS: 200-232-4
• Product Categories: Amino Acids 13C, 2H, 15N;Amino Acids & Derivatives;Intermediates & Fine Chemicals;Neurochemicals;Pharmaceuticals
• Mol File: 55-40-3.mol
• Article Data: 3

Chemical Properties

• Melting Point: 300-301 °C (decomp)
• Boiling Point: 441.6°Cat760mmHg
• Flash Point: 220.9°C
• Appearance: /
• Density: 1.403g/cm³
• Storage Temp.: −20°C
• Solubility: DMSO (Slightly), Water (Slightly)
• PKA: 2.28±0.26(Predicted)
• CAS DataBase Reference: 2-METHYL-3-(3,4-DIHYDROXYPHENYL)-DL-ALANINE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-METHYL-3-(3,4-DIHYDROXYPHENYL)-DL-ALANINE(55-40-3)
• EPA Substance Registry System: 2-METHYL-3-(3,4-DIHYDROXYPHENYL)-DL-ALANINE(55-40-3)

Safety Data

• Hazard Codes: Xi
• Statements: 36
• Safety Statements: 26-36/37
• WGK Germany: 3
• Hazardous Substances Data: 55-40-3(Hazardous Substances Data)

Usage

Chemical Properties

Grey Solid

Synthetic route

DL-N-Acetyl-α-methyl-β-<3,4-dimethoxy-phenyl>-alanin (5934-66-7) → alpha-methyldopa (55-40-3)

Conditions	Yield
(hydrolysis);

2-Amino-3-(3,4-bis-benzyloxy-phenyl)-2-methyl-propionic acid ethyl ester; hydrochloride (84713-76-8) → alpha-methyldopa (55-40-3)

Conditions	Yield
With hydrogenchloride; hydrogen; palladium on activated charcoal 1.) ethanol; Yield given. Multistep reaction;

(+-)-2-amino-3-<3.4-dimethoxy-phenyl>-2-methyl-propionic acid → alpha-methyldopa (55-40-3)

Conditions	Yield
With hydrogen bromide

(+-)-2-amino-3-<3-hydroxy-4-methoxy-phenyl>-2-methyl-propionic acid → alpha-methyldopa (55-40-3)

Conditions	Yield
With hydrogenchloride

L-Dopa ethyl ester hydrochloride (23234-41-5) → alpha-methyldopa (55-40-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 2.) K2CO3 / 2.) Acetone 2: 1.) solid KOH 2.) 1N HCl / 1.) tetrabutylammonium iodide / 1.) acetonitrile, 0 to 15 deg C 2.) ether, 0 deg C. 3: 1.) hydrogen 2.) 6N HCl / 1.) 10 percent Pd/C / 1.) ethanol View Scheme

3-(3,4-Bis-benzyloxy-phenyl)-2-{[1-(2,4,6-trimethyl-phenyl)-meth-(Z)-ylidene]-amino}-propionic acid ethyl ester (84713-73-5) → alpha-methyldopa (55-40-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) solid KOH 2.) 1N HCl / 1.) tetrabutylammonium iodide / 1.) acetonitrile, 0 to 15 deg C 2.) ether, 0 deg C. 2: 1.) hydrogen 2.) 6N HCl / 1.) 10 percent Pd/C / 1.) ethanol View Scheme

(±)-3-(3,4-dimethoxyphenyl)-2-amino-2-methylpropanenitrile (2543-46-6) → alpha-methyldopa (55-40-3)

Conditions	Yield
With water; hydrogen bromide

1-Fluoro-2-isocyanato-benzene (16744-98-2) + alpha-methyldopa (55-40-3) → 3-(3,4-dihydroxyphenyl)-2-(3-(2-fluorophenyl)ureido)-2-methylpropanoic acid

Conditions	Yield
With triethylamine In tetrahydrofuran at 40 - 50℃; for 3h; Catalytic behavior; Reagent/catalyst; Solvent;	90%

alpha-methyldopa (55-40-3) + 4-bromophenyl isocyanate (2493-02-9) → (3-(4-bromophenyl)ureido)-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid

Conditions	Yield
With triethylamine In tetrahydrofuran at 40 - 50℃; for 3h;	90%

alpha-methyldopa (55-40-3) + o-trifluoromethyl-phenylisocyanate (2285-12-3) → 3-(3,4-dihydroxyphenyl)-2-methyl-2-(3-(2-(trifluoromethyl)phenyl)ureido)propanoic acid

Conditions	Yield
With triethylamine In tetrahydrofuran at 40 - 50℃; for 3h;	90%

alpha-methyldopa (55-40-3) + 4-chloro-3-(trifluoromethyl)phenyl isocyanate (327-78-6) → 2-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid

Conditions	Yield
With triethylamine In tetrahydrofuran at 40 - 50℃; for 3h;	90%

alpha-methyldopa (55-40-3) + m-chlorophenyl isocyanate (2909-38-8) → 2-(3-(3-chlorophenyl)ureido)-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid

Conditions	Yield
With triethylamine In tetrahydrofuran at 40 - 50℃; for 3h;	90%

cis-dichlorobis(triphenylphosphine)platinum(II) (10199-34-5, 14056-88-3, 15604-36-1) + alpha-methyldopa (55-40-3) → Pt(P(C6H5)3)2(O2C6H3CH2CCH3(NH2)COOH)*0.5CH2Cl2

Conditions	Yield
With potassium hydroxide; dichloromethane In methanol; benzene to a suspn. of substituted catechol in benzene was added MeOH soln. of KOH; prepd. soln. was syringed into suspn. of Pt complex in benzene; stirring at room temp. for 3.5 h (Ar); filtration, evapn., washing with water, drying in vac., dissoln. in CH2Cl2, filtration, evapn., washing with ether, drying in vac.; elem. anal.;	84%

alpha-methyldopa (55-40-3) + chloroacetyl chloride (79-04-9) → N-Chloroacetyl-α-methyl-DOPA (121704-32-3)

Conditions	Yield
In acetonitrile for 1.5h; Heating;	60%

1-chloroethyl pivalate (40258-80-8) + alpha-methyldopa (55-40-3) → α-methyldopa pivaloylethyl ester (81660-38-0) + 3-(3,4-Dihydroxy-phenyl)-2-[1-(2,2-dimethyl-propionyloxy)-ethylamino]-2-methyl-propionic acid 1-(2,2-dimethyl-propionyloxy)-ethyl ester (102108-09-8)

Conditions	Yield
With 4 A molecular sieve In various solvent(s) at 75℃; for 8h; Product distribution; other temperature, various solvents; other alkylating agents; other amino acids; with or without LiBr;

alpha-methyldopa (55-40-3) → 2-Amino-3-(3,4-dioxo-cyclohexa-1,5-dienyl)-2-methyl-propionic acid (73688-25-2)

Conditions	Yield
With phenoloxidase from Lucilia cuprina pupae Enzyme kinetics; Oxidation;
With oxygen In phosphate buffer at 20℃; pH=6.8; Enzyme kinetics; Further Variations:; Reagents;

alpha-methyldopa (55-40-3) → α-methyldopachrome (131923-54-1)

Conditions	Yield
With sodium periodate In phosphate buffer for 0.166667h; pH=6.0; Oxidation; cyclization;

4-amino-2,3-dimethyl-1-phenylpyrazolin-5-one (83-07-8) + alpha-methyldopa (55-40-3) + potassium hexacyanoferrate(III) → [Fe(HOC6H2(O)(CH2C(CH3)(NH2)COOH)NHCC(O)N(C6H5)N(CH3)C(CH3))2(CN)(H2O)] (753453-85-9)

Conditions	Yield
In water hot aq. soln. of catecholamine was mixed with hot aq. soln. of 4-aminoantipyrine (60°C); mixt. was mixed with stirring with hot soln. of Fe compd. (60°C); mixt. was kept at room temp. for 6 h; filtered; washed (H2O, pentane); collected; dried in vac. over CaCl2; elem. anal.;

4-amino-2,3-dimethyl-1-phenylpyrazolin-5-one (83-07-8) + alpha-methyldopa (55-40-3) + copper(II) sulfate (7758-99-8) → [Cu(O2C6H2(CH2C(CH3)(NH2)COOH)NHCC(O)N(C6H5)N(CH3)C(CH3))(H2O)2]*4H2O

Conditions	Yield
With ammonia In water ammonia soln. was added dropwise with stirring to soln. of Cu salt; hot (60°C) aq. soln. of catecholamine and hot (60°C) aq. soln.of 4-aminoantipyrine were added with stirring; concd.; kept in cupboard; filtered; washed (H2O, pentane); collected; dried in vac. over CaCl2; elem. anal.;

alpha-methyldopa (55-40-3) + o-phthalic dicarboxaldehyde (643-79-8) → C28H28N2O8

Conditions	Yield
Stage #1: alpha-methyldopa With potassium hydroxide In methanol; ethanol for 1h; Stage #2: o-phthalic dicarboxaldehyde In methanol; ethanol for 2h;

alpha-methyldopa (55-40-3) + o-phthalic dicarboxaldehyde (643-79-8) → C28H30CrN2O10*H2O

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium hydroxide / methanol; ethanol / 1 h 1.2: 2 h 2.1: methanol / 2 h / Reflux View Scheme

manganese(II) chloride hydrate + alpha-methyldopa (55-40-3) + aspirin (50-78-2) → C19H23MnNO10

Conditions	Yield
With potassium hydroxide In ethanol for 2h; Heating;

iron(II) chloride hydrate + alpha-methyldopa (55-40-3) + aspirin (50-78-2) → C19H23FeNO10

Conditions	Yield
With potassium hydroxide In ethanol for 2h; Heating;

cobalt(II) chloride hydrate + alpha-methyldopa (55-40-3) + aspirin (50-78-2) → C19H23CoNO10

Conditions	Yield
With potassium hydroxide In ethanol for 2h; Heating;

nickel(II) dichloride hydrate + alpha-methyldopa (55-40-3) + aspirin (50-78-2) → C19H23NNiO10

Conditions	Yield
With potassium hydroxide In ethanol for 2h; Heating;

copper(II) chloride hydrate + alpha-methyldopa (55-40-3) + aspirin (50-78-2) → C19H23CuNO10

Conditions	Yield
With potassium hydroxide In ethanol for 2h; Heating;

manganese(II) chloride hydrate + 4-acetaminophenol (103-90-2) + alpha-methyldopa (55-40-3) → C18H24MnN2O8

Conditions	Yield
With potassium hydroxide In ethanol for 2h; Heating;

iron(II) chloride hydrate + 4-acetaminophenol (103-90-2) + alpha-methyldopa (55-40-3) → C18H24FeN2O8

Conditions	Yield
With potassium hydroxide In ethanol for 2h; Heating;

Upstream product

• 2543-46-6 (±)-3-(3,4-dimethoxyphenyl)-2-amino-2-methylpropanenitrile 
• 84713-73-5 3-(3,4-Bis-benzyloxy-phenyl)-2-{[1-(2,4,6-trimethyl-phenyl)-meth-(Z)-ylidene]-amino}-propionic acid ethyl ester 
• 23234-41-5 L-Dopa ethyl ester hydrochloride 
• 84713-76-8 2-Amino-3-(3,4-bis-benzyloxy-phenyl)-2-methyl-propionic acid ethyl ester; hydrochloride 
• 5934-66-7 DL-N-Acetyl-α-methyl-β-<3,4-dimethoxy-phenyl>-alanin 

Downstream Products

• 73688-25-2 2-Amino-3-(3,4-dioxo-cyclohexa-1,5-dienyl)-2-methyl-propionic acid 
• 121704-32-3 N-Chloroacetyl-α-methyl-DOPA 
• 81660-38-0 α-methyldopa pivaloylethyl ester 
• 102108-09-8 3-(3,4-Dihydroxy-phenyl)-2-[1-(2,2-dimethyl-propionyloxy)-ethylamino]-2-methyl-propionic acid 1-(2,2-dimethyl-propionyloxy)-ethyl ester 
• 753453-85-9 [Fe(HOC₆H₂(O)(CH₂C(CH₃)(NH₂)COOH)NHCC(O)N(C₆H₅)N(CH₃)C(CH₃))2(CN)(H₂O)] 

Relevant articles and documents

Multiple molecular targets mediated antioxidant activity, molecular docking, ADMET, QSAR and bioactivity studies of halo substituted urea derivatives of α-Methyl-L-DOPA

A series of novel α-methyl-L-DOPA urea derivatives viz., 3-(3,4-dihydroxyphenyl)-2-methyl-2-(3-halo/trifluoromethyl substituted phenyl ureido)propanoic acids (6a-e) have been synthesized from the reaction of α-methyl-L-DOPA (3) with various aryl isocyanates (4a-e) by using triethylamine (5, TEA) as a base catalyst in THF at reflux conditions. The synthesized compounds are structurally characterized by spectral (IR, 1H & 13C NMR and MASS) and elemental analysis studies and screened for their in-vitro antioxidant activity against DPPH, NO and H2O2 free radical scavenging assays and identified compounds 6c & 6d as potential antioxidants. The acquired in vitro results were correlated with the results of molecular docking, ADMET, QSAR and bioactivity studies performed for them and predicted that the recorded in silico binding affinities are in good correlation with the in vitro antioxidant activity results. The molecular docking analysis has comprehended the strong hydrogen bonding interactions of 6a-e with 1CB4, 1N8Q, 3MNG, 1OG5, 1DNU, 3NRZ, 2CDU, 1HD2 and 2HCK proteins of their respective SOD, LO, PRXS5, CP450, MP, XO, NO, PRY5 and HCK enzymes. This has sustained the effective binding of 6a-e and resulted in functional inhibition of selective aminoacid residues to be pronounced as multiple molecular targets mediated antioxidant potent compounds. In addition, the evaluated toxicology risks of 6a-e are identified with in the potential limits of drug candidates. The conformational analysis of 6c & 6d prominently infers that urea moiety uniting α-methyl-L-DOPA with halo substituted aryl units into a distinctive orientation to comply good structure-activity to inhibit the proliferation of reactive oxygen species in vivo.

Studies on optically active amino acids. VI. Studies on alpha-alkyl-alpha-amino acids. II. Resolution of some alpha-methyl-alpha-amino acids through 1-menthyl ester.

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