42856-71-3

Basic information

• Product Name: (S)-2-Methylproline
• Synonyms: (S)-2-Methyl proline;(2s,5s)-5-Methylpyrrolidine-2-Carboxylic Acid;5-Methyl-L-Proline;(2S)-2-Methylpyrrolidin-2-ylcarboxylic acid;L-Proline, 2-methyl- (9CI);(S)-2-methylpyrrolidine-2-carboxylic acid;α-methyl-l-proline;2-methylproline
• CAS NO: 42856-71-3
• Molecular Formula: C₆H₁₁NO₂
• Molecular Weight: 129.16
• EINECS: 1592732-453-0
• Product Categories: GLYCINESCAFFOLD;Peptide Synthesis;Proline Derivatives;Unnatural Amino Acid Derivatives
• Mol File: 42856-71-3.mol

Chemical Properties

• Melting Point: 310°C(lit.)
• Boiling Point: 241.9 °C at 760 mmHg
• Flash Point: 100.1 °C
• Appearance: /
• Density: 1.119 g/cm³
• Vapor Pressure: 0.0116mmHg at 25°C
• Refractive Index: 1.475
• Storage Temp.: -15°C
• Solubility: soluble in Methanol
• PKA: 2.44±0.20(Predicted)
• BRN: 4350211
• CAS DataBase Reference: (S)-2-Methylproline(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-2-Methylproline(42856-71-3)
• EPA Substance Registry System: (S)-2-Methylproline(42856-71-3)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 3
• Hazardous Substances Data: 42856-71-3(Hazardous Substances Data)

Usage

Chemical Properties

White powder

InChI:InChI=1/C6H11NO2/c1-6(5(8)9)3-2-4-7-6/h7H,2-4H2,1H3,(H,8,9)/t6-/m1/s1

Upstream product

• 5891-21-4 5-chloro-2-pentanone 
• 1415303-32-0 (2S,1'S)-N-(1'-phenylethyl)-α-methylprolinamide (S)-mandelic acid salt 
• 42457-13-6 2-cyano-2-methylpyrrolidine 
• 1361112-89-1 2-methylpyrrolidine-2-carboxamide hydrochloride 
• 66856-17-5 2-amino-5-hydroxy-2-methylpentanoic acid 
• 160187-05-3 (S)-2-amino-5-hydroxy-2-methylpentanoic acid 
• 147-85-3 L-proline 
• 118916-60-2 (2R,5S)-2-trichloromethyl-1-aza-3-oxabicyclo[3.3.0]octan-4-one 
• 1415303-35-3 1-(carbamoyl phenylmethyl)-2-cyano-2-methylpyrrolidine 
• 103336-06-7 N-(tert-butoxycarbonyl)-2-methyl-L-proline 
• 1415303-22-8 (2S,1'S)-N-(1'-phenylethyl)-α-methylprolinamide 
• 111080-58-1 1-benzyl-2-methylpyrrolidine-2-carboxamide 
• 1310563-79-1 1-benzyl-2-methylpyrrolidine-2-carbonitrile 

Downstream Products

• 88958-64-9 1-(4-nitrophenyl)-1-hydroxy-3-butanone 
• 1001353-78-1 (S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-2-methylpyrrolidine-2-carboxylic acid 
• 103336-06-7 N-(tert-butoxycarbonyl)-2-methyl-L-proline 
• 144412-46-4 1-(p-cyanobenzoyl)-2-methyl-L-proline 
• 1339022-10-4 tert-butyl (2S)-2-(hydroxymethyl)-2-methylpyrrolidine-1-carboxylate 
• 152722-89-9 (2R,4R)-4-Hydroxy-2-methylprolin 
• 1261569-85-0 (S)-8a-methyloctahydropyrrolo[1,2-a]pyrazine 
• 847952-36-7 (8aS)-8a-methylhexahydropyrrolo[1,2-a]pyrazine-1,4-dione 
• 1374892-64-4 (S)-2-methyl-pyrrolidine-1,2-dicarboxylic acid 1-methyl ester 

Relevant articles and documents

Preparation method of optically active 2-methylproline

The invention discloses a preparation method of optically active 2-methylproline. According to the method, 5-hydroxy-2-pentanone (formula 1) is taken as a starting material to be subjected to condensation with a cyaniding reagent; hydrolysis is carried out so as to obtain 2-amino-5-hydroxy-2-methylvaleric acid (formula 2); 2-amino-5-hydroxy-2-methylvaleric acid (formula 2) and a resolving agent are subjected to salifying precipitation, followed by ph regulation and precipitation so as to obtain 2-amino-5-hydroxy-2-methylvaleric acid (formula 4) with optical activity; the compound as shown in formula 4 is protected with an amino protective agent to obtain a compound as shown in formula 5; the compound as shown in formula 5 is chlorinated with a chlorinating reagent while removing an amino protective group to obtain a compound as shown in formula 6; and one-pot cyclization is carried out to obtain the optically active 2-methylproline (formula 7). The preparation method is high in comprehensive yield, low in cost, mild in reaction condition and easy for large-scale production.

A Designed Approach to Enantiodivergent Enamine Catalysis

The rational design and implementation of enantiodivergent enamine catalysis is reported. A simple secondary amine catalyst, 2-methyl-l-proline, and its tetrabutylammonium salt function as an enantiodivergent catalyst pair delivering the enantiomers of α-functionalized aldehyde products in excellent enantioselectivities. This novel concept of designed enantiodivergence is applied to the enantioselective α-amination, aldol, and α-aminoxylation/α-hydroxyamination reactions of aldehydes.

Α-substd. provitamin optically active production of phosphorus

PROBLEM TO BE SOLVED: To provide an industrial method practically suitable for producing an optically active α-substituted prolines with short process and mild conditions.SOLUTION: A method of producing an optically active α-substituted prolines (6) includes (d) a step of obtaining an optically active N, α-substituted prolines (5) by hydrolysis of an optically active N, α-substituted proline amides (4), and (e) a step of obtaining an optically active α-substituted prolines (6) by eliminating the optically active N, and a protective group Rof the α-substituted prolines (5).

METHOD FOR PRODUCING OPTICALLY ACTIVE ALPHA-SUBSTITUTED PROLINE

The present invention aims to provide an industrial method practically suitable for producing optically active α-substituted prolines from an acyclic ketone compound by a small number of steps under mild conditions. The present invention relates to a production method of an optically active α-substituted proline (4) and/or an optically active α-substituted prolinamide (5), including (a) reacting an acyclic ketone compound (1) with at least one selected from ammonia, an ammonium salt, primary amine and a salt of primary amine, and a cyanating agent to give a cyclic nitrogen-containing compound (2), (b) hydrating the cyclic nitrogen-containing compound (2) to give an α-substituted prolinamide (3), and (c) resolving the α-substituted prolinamide (3) by one or more of (d) enzymatical hydrolysis, (e) resolution by diastereomeric salt formation, and (f) separation by column chromatography.

PROCESS FOR PRODUCING SOLID AMINO ACID

The problem to be solved by the present invention is to ea lily and efficiently produce an amino acid having 2 to 7 carbon atoms as a high-purity solid without complicated operation, which is useful as a synthetic intermediate for medicines or agrochemicals. The present invention is characterized in comprising a step of precipitating solid amino acid with high purity. In the present invention, the by-produced salt composed of the sulfonic acid and the amine was removed to the mother liquor by reacting an amine with a sulfonic acid salt of amino acid in an aprotic polar solvent, or by reacting a sulfonic acid with an amine salt of amino acid in an aprotic polar solvent. The sulfonic acid salt of amino acid, for example, may be produced by reacting a N-(tert-butoxycarbonyl) amino acid with a sulfonic acid, or by reacting an amino acid tert-butyl ester with a sulfonic acid.

Use of (S)-5-(2-methylpyrrolidin-2-yl)-1H-tetrazole as a novel and enantioselective organocatalyst for the aldol reaction

The novel organocatalyst (S)-5-(2-methylpyrrolidin-2-yl)-1H-tetrazole (4) catalyzes the aldol reaction between acetone and various aldehydes with superior enantioselectivity to the existing organocatalysts (S)-proline (1) and (S)-5-(Pyrrolidin-2-yl)-1H-tetrazole (3). Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Catalytic asymmetric Michael reaction under phase-transfer catalysis: Construction of chiral tetrasubstituted carbon and its application to the synthesis of a chiral pyrrolidone

A catalytic asymmetric Michael reaction using Schiff bases promoted by D2-symmetrical ammonium salts as phase-transfer catalysts is described. The reaction of glycine Schiff base (1a) gave the Michael adduct with up to 91% ee and tetrasubstituted carbons was also constructed using alanine Schiff base (3a) with up to 63% ee.

Highly enantioselective synthesis of rigid, quaternary 1,4-benzodiazepine- 2,5-diones derived from proline

(Chemical Equation Presented) Proline-derived 1,4-benzodiazepine-2,5-diones are extremely useful scaffolds in medicinal chemistry. In this paper, we describe a protocol for retentive C3 alkylation of these materials, thus accomplishing the direct synthesis of enantiopure quaternary 1,4-benzodiazepine-2,5-diones. The high enantioselectivities (up to 99.5%) are attributed to memory of chirality.

Chiral 3,6-dihydro-2H-1,4-oxazin-2-ones as alanine equivalents for the asymmetric synthesis of α-methyl α-amino acids (AMAAs) under mild reaction conditions

3,6-Dihydro-2H-1,4-oxazin-2-ones 1 act as very reactive chiral cyclic alanine equivalents and can be diastereoselectively alkylated or allylated using mild reaction conditions: potassium carbonate under phase-transfer catalysis (PTC) conditions when using activated alkyl halides, organic bases such as tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2- diazaphosphorine (BEMP) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) when using unactivated alkyl halides, and neutral Pd(0)-catalysis when allylic carbonates are used. In most cases, the diastereoselectivity under all these different reaction conditions is excellent although the reactions are always carried out at room temperature. Hydrolysis of the obtained alkylated or allylated oxazinones allows the preparation of enantiomerically enriched (S)- α-methyl α-amino acids (S)-AMAAs. The PTC and organic base methodologies have also been applied to the synthesis of (R)-α-methyl α-amino acids starting from (R)-alanine. When dihalides are used as electrophiles under PTC or BEMP conditions, a spontaneous N-alkylation also takes place giving bicyclic oxazinones, which can be hydrolyzed to enantiomerically pure cyclic (S)-AMAAs.

Asymmetric synthesis of (S)-α-methyl α-amino acids by alkylation of chiral 3,6-dihydro-2h-1,4-oxazin-2-ones using unactivated alkyl halides and organic bases

3,6-Dihydro-2H-1,4-oxazin-2-ones 1 have been diastereoselectively (>96% de) alkylated using unactivated alkyl halides and organic bases such as 2- tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (BEMP) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) at room temperature in the presence of LiI. Hydrolysis of the resulting alkylated systems afforded enantiomerically enriched (S)-α-methyl α-amino acids. When 1,3- diiodopropane was used, spontaneous N-alkylation also took place giving bicyclic oxazinone 6 which was hydrolyzed to (S)-α-methylproline.