101930-07-8

Basic information

• Product Name: (R)-(+)-1-Benzyl-3-pyrrolidinol
• Synonyms: (R)-3-HYDROXYPYRROLIDINE, N-BENZYL;(r)-3-hydroxy-1-benyzl-pyrrolidine;(R)-3-HYDROXY-1-BENZYL-PYRROLIDINE;(R)-1-BENZYL-PYRROLIDIN-3-OL;(R)-1-N-BENZYL-3-HYDROXYPYRROLIDINE;(R)-(+)-1-BENZYL-3-PYRROLIDINOL;(R)-1-BENZYL-3-PYRROLIDINOL;(R)-1-BENZYL-3-HYDROXYPYRROLIDINE
• CAS NO: 101930-07-8
• Molecular Formula: C₁₁H₁₅NO
• Molecular Weight: 177.24
• EINECS: 212-273-5
• Product Categories: Pyrrole&Pyrrolidine&Pyrroline;Benzenes;Chiral Building Blocks;Simple Alcohols (Chiral);Synthetic Organic Chemistry;Chiral Building Blocks;Heterocyclic Building Blocks;Pyrrolidines
• Mol File: 101930-07-8.mol

Chemical Properties

• Boiling Point: 116 °C0.9 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: /
• Density: 1.07 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.000592mmHg at 25°C
• Refractive Index: n20/D 1.548(lit.)
• Storage Temp.: 2-8°C
• PKA: 14.82±0.20(Predicted)
• CAS DataBase Reference: (R)-(+)-1-Benzyl-3-pyrrolidinol(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-(+)-1-Benzyl-3-pyrrolidinol(101930-07-8)
• EPA Substance Registry System: (R)-(+)-1-Benzyl-3-pyrrolidinol(101930-07-8)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-37/39
• WGK Germany: 3
• Hazardous Substances Data: 101930-07-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(R)-(+)-1-Benzyl-3-pyrrolidinol is used as a chiral building block for the synthesis of pharmaceutical compounds. Its unique structure allows for the creation of beta-proline-like derivatives, which act as sodium channel blockers, playing a crucial role in the development of medications targeting neurological disorders and other conditions.
Used in Biologically Active Compounds Synthesis:
In the field of biologically active compounds, (R)-(+)-1-Benzyl-3-pyrrolidinol is utilized as a precursor for the synthesis of molecules with potential therapeutic applications. Its versatility in chemical reactions enables the production of a wide range of bioactive substances, contributing to advancements in medicine and healthcare.

InChI:InChI=1/C11H15NO/c13-11-6-7-12(9-11)8-10-4-2-1-3-5-10/h1-5,11,13H,6-9H2/t11-/m1/s1

Upstream product

• 6913-92-4 1-benzyl-2,5-dihydro-1H-pyrrole 
• 116143-02-3 (3R)-1-(phenylmethyl)pyrrolidin-3-ol Acetate 
• 101469-91-4 (3S)-1-benzyl-3-hydroxypyrrolidine-2,5-dione 
• 156150-59-3 (R)-(+)-3-(acetoxy)-1-(phenylmethyl)-2,5-pyrrolidinedione 
• 40499-83-0 (3R)-pyrrolidinol 
• 100-52-7 benzaldehyde 
• 29897-82-3 N-benzylpyrrolidine 
• 100-39-0 benzyl bromide 
• 118354-71-5 (S)-methanesulfonic acid 1-benzylpyrrolidin-3-yl ester 
• 100-46-9 benzylamine 
• 116183-79-0 (3S)-3-<(4-tolylsulfonyl)oxy>-1-(phenylmethyl)pyrrolidine 
• 100-44-7 benzyl chloride 
• 104706-47-0 (R)-3-hydroxypyrrolidine hydrochloride 
• 1104643-29-9 (R)-3-tert-butoxy-N-benzylpyrrolidine 

Downstream Products

• 104831-94-9 (3S)-1-benzyl-3-pyrrolidinyl methyl (4R)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride 
• 104757-55-3 (3R)-1-benzyl-3-pyrrolidinyl methyl (4R)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride 
• 114715-35-4 (R)-3-methanesulfonyloxy-1-(phenylmethyl)-pyrrolidine 
• 116183-80-3 (3R)-3-<(4-tolylsulfonyl)oxy>-1-(phenylmethyl)pyrrolidine 
• 40499-83-0 (3R)-pyrrolidinol 
• 109431-87-0 (R)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate 
• 315191-14-1 Hydroxy-diphenyl-acetic acid (R)-1-benzyl-pyrrolidin-3-yl ester 
• 895148-86-4 (S)-3-(1-benzyl-pyrrolidin-3-yl)-5,5-diphenyl-imidazolidine-2,4-dione 
• 131852-53-4 (S)-1-benzyl-3-(tert-butoxycarbonylamino)pyrrolidine 
• 213008-26-5 (3S)-1-benzyl-3-[(5-methoxy-2,3-dihydro-1H-inden-4-yl)oxy]tetrahydro-1H-pyrrole 
• 127423-61-4 tert-butyl (3R)-3-methylsulfonyloxypyrrolidine-1-carboxylate 
• 177947-67-0 (3R)-N-(tert-butyloxycarbonyl)-3-(benzyloxy)pyrrolidine 
• 199336-82-8 (R)-3-(N-Benzyl-N-methylamino)pyrrolidine-1-carboxylic acid tert-butyl ester 
• 719278-73-6 (3S)-1-benzylpyrrolidin-3-yl-(2R)-cyclopentyl(hydroxy)phenyl acetate 

Relevant articles and documents

Exploring Derivatives of Quinazoline Alkaloid l-Vasicine as Cap Groups in the Design and Biological Mechanistic Evaluation of Novel Antitumor Histone Deacetylase Inhibitors

l-Vasicine is a quinazoline alkaloid with an electron dense ring and additional functionalities in its structure. Employing target oriented synthesis (TOS) based on in silico studies, molecules with significant docking scores containing different derivatives of l-vasicine as caps were synthesized. Interestingly, one molecule, i.e., 4a, which contained 3-hyroxypyrrolidine as a cap group and a six carbon long aliphatic chain as a linker was found to inhibit HDACs. 4a showed more specificity toward class I HDAC isoforms. Also 4a was found to be less cytotoxic toward normal cell lines as compared to cancer cell lines. 4a inhibited cancer cell growth and induced cell death by various mechanisms. However, 4a was found to induce cell death independent of ROS generation, and unlike many natural product based HDAC inhibitors, 4a was found to be nontoxic under in vivo conditions. Importantly, we for the first time report the possibility of using a 3-hydroxypyrrolidine cap for the synthesis of HDAC inhibitors with good potency.

Stereo-complementary bioreduction of saturated N-heterocyclic ketones

The asymmetric bioreduction of several saturated N-heterocyclic ketones is demonstrated in a stereo-complementary fashion using the ketoreductases READH and ChKRED20 for the production of (S)- and (R)-alcohols, respectively. The reaction accepts substrates with a five-, six- or seven-membered ring, and exhibits excellent stereoselectivity when using 2-propanol as both the ultimate reducing agent and cosolvent, achieve >99% ee in the majority of cases for both enantiomers.

Preparation of enantiomerically pure N-heterocyclic amino alcohols by enzymatic kinetic resolution

Abstract The synthesis of both enantiomers of N-benzyl-3-hydroxypyrrolidine and N-benzyl-3-hydroxypiperidine via enzymatic kinetic resolution of the corresponding racemic esters is described. Various commercially available hydrolases were studied as biocatalysts in native and immobilized form. The best results were obtained with lipases PS, AK, CAL-B and with protease Alcalase, which were active and selective for the kinetic resolutions of racemic esters (E > 100). Under optimized reaction conditions, highly enantiomerically enriched (up to 99.5% ee) resolution products were obtained. Lipase and protease showed opposite enantiopreference on the esters, allowing the preparation of both enantiomers of the target compounds. Semi-continuous reactions in column reactors with immobilized biocatalysts were also performed with high enantioselectivities. Inversion of the configuration at C(3) of N-benzyl-3-hydroxypyrrolidine was quantitatively effected in a short number of steps.

3-Hydroxypyrrolidine and (3,4)-dihydroxypyrrolidine derivatives: Inhibition of rat intestinal α-glucosidase

Thirteen pyrrolidine-based iminosugar derivatives have been synthesized and evaluated for inhibition of α-glucosidase from rat intestine. The compounds studied were the non-hydroxy, mono-hydroxy and dihydroxypyrrolidines. All the compounds were N-benzylated apart from one. Four of the compounds had a carbonyl group in the 2,5-position of the pyrrolidine ring. The most promising iminosugar was the trans-3,4-dihydroxypyrrolidine 5 giving an IC50 of 2.97 ± 0.046 and a KI of 1.18 mM. Kinetic studies showed that the inhibition was of the mixed type, but predominantly competitive for all the compounds tested. Toxicological assay results showed that the compounds have low toxicity. Docking studies showed that all the compounds occupy the same region as the DNJ inhibitor on the enzyme binding site with the most active compounds establishing similar interactions with key residues. Our studies suggest that a rotation of ～90° of some compounds inside the binding pocket is responsible for the complete loss of inhibitory activity. Despite the fact that activity was found only in the mM range, these compounds have served as simple molecular tools for probing the structural features of the enzyme, so that inhibition can be improved in further studies.

Natural (-)-vasicine as a novel source of optically pure 1-benzylpyrrolidin-3-ol

A facile and scalable methodology for the preparation of optically active (3S)-1-benzylpyrrolidin-3-ol (3), an important drug precursor, is reported. Starting from the naturally occurring alkaloid (-)-vasicine (1), a major alkaloid of the plant Adhatoda vasica, 3 was obtained in 84% overall yield (Scheme 3). Copyright

PROCESS FOR THE PREPARATION OF OPTICALLY ACTIVE N-BENZYL-3 HYDROXYPYRROLIDINES

The present invention relates to a facile, highly efficient and economical process for the preparation of optically active N-benzyl-3-hydroxypyrrolidine in high yield from a naturally occurring alkaloid vasicine. The natural alkaloid vasicine is used as a precursor of (S)—N-benzyl-3-hydroxypyrrolidine and (R)—N-benzyl-3-hydroxypyrrolidines which can easily be sourced from the medicinal plant Adatoda vasica by the method known in the art and transformed to optical isomers (R) and (S)—N-benzyl-3-hydroxypyrrolidine by the method described in the present invention.

Evolving P450pyr hydroxylase for highly enantioselective hydroxylation at non-activated carbon atom

Directed evolution of a monooxygenase to achieve very high enantioselectivity for hydroxylation at non-activated carbon atoms is demonstrated for the first time, where a triple mutant of P450pyr hydroxylase is obtained via determination of enzyme structure, iterative saturation mutagenesis, and high-throughput screening with a MS-based ee assay to increase the product ee from 53% to 98% for the hydroxylation of N-benzyl pyrrolidine to (S)-N-benzyl 3-hydroxypyrrolidine. The Royal Society of Chemistry 2012.

A study on the racemization step in the synthesis of pyrrolidinols via cyclic α-hydroxyimides

Analytical HPLC methods for the determination of the enantiomeric excess of N-protected malimides 1 as well as the corresponding pyrrolidinol 5 and tartarimides 2 and 3 have been established. On this basis, a study to reveal the racemization step in the synthesis of pyrrolidinols from α-hydroxyacids, via chiral cyclic α-hydroxyimides, has been undertaken. It was confirmed that the known, one-step method for the synthesis of the N-protected chiral cyclic imides from α-hydroxydiacids proceeded with little racemization, and partial racemization has been proven to occur during the reduction of the resultant imide 1a with LAH to yield the corresponding pyrrolidinol 5. Conditions have been defined in order to avoid racemization in the LAH reduction step.

A PROCESS FOR THE PREPARATION OF OPTICALLY ACTIVE N-BENZYL-3 HYDROXYPYRROLIDINES

The present invention relates to a facile, highly efficient and economical process for the preparation of optically active N-benzyl-3-hydroxypyrrolidine in high yield from a naturally occurring alkaloid vasicine. The natural alkaloid vasicine is used as a precursor of (S)-N-benzyl-3-hydroxypyrrolidine and (R)-N-benzyl-3-hydroxypyrrolidines which can easily be sourced from the medicinal plant Adatoda vasica by the method known in the art and transformed to optical isomers (R) and (S)-N-benzyl-3-hydroxypyrrolidine by the method described in the present invention.

Inverting the enantioselectivity of P450pyr monooxygenase by directed evolution

We report the first example of directed evolution of a P450 monooxygenase with inverted enantioselectivity for asymmetric biohydroxylation. The biohydroxylation product of the best mutant 1AF4A has an ee of 83% (R) compared to the wild type's ee of 43% (S). The Royal Society of Chemistry 2010.