53310-83-1

Upstream product

• 53310-82-0 (S)-1-ethoxycarbonyl-2-(p-toluenesulfonyloxymethyl)pyrrolidine 
• 53310-86-4 (S)-2-(4-bromo-benzenesulfonyloxymethyl)-pyrrolidine-1-carboxylic acid methyl ester 
• 75-44-5 phosgene 
• 23356-96-9 (S)-1-Pyrrolidin-2-yl-methanol 
• 69610-40-8 N-(tert-butoxycarbonyl)-L-prolinol 
• 530-62-1 1,1'-carbonyldiimidazole 
• 147-85-3 L-proline 
• 59936-29-7 (S)-N-(tert-butoxycarbonyl)proline methyl ester 
• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 332-25-2 4-(trifluoromethoxy)benzonitrile 
• 616-38-6 carbonic acid dimethyl ester 
• 192456-74-9 (S)-tetrahydropyrrolo[1,2-c]oxazole-3(1H)-thione 
• 1004-09-7 (rac)-sodium 1-phenylethanolate 
• 201230-82-2 carbon monoxide 

Downstream Products

• 106865-52-5 (S)-(+)-2-[(phenylthio)methyl]pyrrolidine 
• 1202398-12-6 (S)-2-(benzylthiomethyl)pyrrolidine 

Relevant academic research and scientific papers

Visible-Light-Mediated Liberation and In Situ Conversion of Fluorophosgene

The first example for the photocatalytic generation of a highly electrophilic intermediate that is not based on radical reactivity is reported. The single-electron reduction of bench-stable and commercially available 4-(trifluoromethoxy)benzonitrile by an organic photosensitizer leads to its fragmentation into fluorophosgene and benzonitrile. The in situ generated fluorophosgene was used for the preparation of carbonates, carbamates, and urea derivatives in moderate to excellent yields via an intramolecular cyclization reaction. Transient spectroscopic investigations suggest the formation of a catalyst charge-transfer complex-dimer as the catalytic active species. Fluorophosgene as a highly reactive intermediate, was indirectly detected via its next downstream carbonyl fluoride intermediate by NMR. Furthermore, detailed NMR analyses provided a comprehensive reaction mechanism including a water dependent off-cycle equilibrium.

PHARMACEUTICAL COMPOUNDS

The invention provides compounds of the formula (1) or salts or tautomers thereof; wherein: Q is SO or SO2; n is 1 or 2; R1 is selected from hydrogen and a non-aromatic C1-6 hydrocarbon group; R2 and R3 are independently selected from hydrogen and a C1-6 hydrocarbon group; or R2 and R3 together with the carbon atom to which they are attached form a carbonyl group (C=O), a cyclopropane-1,1-diyl group or a cyclobutane-1,1-diyl group; or R together with R2 forms a C2-4 alkylene linker which is optionally substituted with one or more substituents selected from a C1-4 hydrocarbon group, halogen, hydroxy and amino; R4 and R5 are independently selected from hydrogen and a non-aromatic C1-6 hydrocarbon group; or R4 and R5 together with the carbon atom to which they are attached form a cyclopropane-1,1-diyl group or a cyclobutane-1,1-diyl group; and Ar1 is selected from phenyl, thiophenyl and furanyl,each being optionally substituted. The compounds are useful in medicine, for example in the treatment of diseases, such as cancers.

Amidation of esters with amino alcohols using organobase catalysis

A catalytic protocol for the base-mediated amidation of unactivated esters with amino alcohol derivatives is reported. Investigations into mechanistic aspects of the process indicate that the reaction involves an initial transesterification, followed by an intramolecular rearrangement. The reaction is highly general in nature and can be extended to include the synthesis of oxazolidinone systems through use of dimethyl carbonate.

Contiguous generation of quaternary and tertiary stereocenters: One-pot synthesis of chroman-fused S-proline-derived chiral oxazepinones

A new class of chroman-fused S-proline-derived chiral oxazepinones has been synthesized in one pot through contiguous generation of quaternary and tertiary stereocenters.

Enzyme-catalyzed enantiomeric resolution of N-Boc-proline as the key-step in an expeditious route towards RAMP

For the preparation of both enantiomers of N-carbamoyl-2-methoxymethylpyrrolidine, the precursors of Enders' chiral auxiliaries, SAMP and RAMP, enzyme-catalyzed kinetic resolution of racemic N-carbamoyl, N-Boc, N-Cbz proline esters and prolinols were examined. B. licheniformis protease (subtilisin) preferentially hydrolyzed the (R)-carbamoylproline ester with an enantiomeric ratio (E) of 10. To a hydrophobic N-Cbz proline ester, subtilisin showed lower selectivity (E=2.8), and in contrast, a purified protease (isozyme A) from the earthworm showed the preference of (S)-enantiomer (E=13.6). In a practical sense, C. antarctica lipase B (Chirazyme L-2) was effective for the hydrolysis of both N-Boc and N-Cbz derivatives with E >100. The e.e. of (R)-N-carbamoyl-2-methoxymethylpyrrolidine was raised to be >99.9% by recrystallization at the N-Boc-prolinol stage, which was derived from the (R)-N-Boc-proline methyl ester (98.7% e.e.) through a preparative-scale enzyme-catalyzed resolution (49% yield) of the racemic substrate.

The reaction of β-amino alcohols with 1,1′ -carbonyldiimidazole - Influence of the nitrogen substituent on the reaction course

The reaction of β-amino alcohols with 1,1′carbonyldiimidazole in dichloromethane is affected by the size of the nitrogen substituent. 1,3-Oxazolidin-2-ones are exclusively obtained from N-H, N-methyl and N-arylmethyl derivatives. O-(1-Imidazolyl)carbonyl derivatives are formed as intermediates from N-[1-(2-pyridyl)alkyl]-(S)-valinol and are mainly or exclusively converted into aziridines in the presence of water, although the cyclization is impeded by large N-substituents such as triphenylmethyl.

Treatment of N-Boc derivatives of β-amino alcohols with N,N- diethylaminosulfur trifluoride leads to chiral oxazolidinones: An unexpected intramolecular cyclization

Chiral 2-oxazolidinones were produced in good yields by treatment of N. tert-butoxycarbonyl derivatives of β-amino alcohols with N,N- Diethylaminosulfur Trifluoride (DAST) under mild reaction conditions. An intramolecular nucleophilic attack mechanism is proposed to explain the formation of the heterocycles.

Stereoselective access to trans-2,5-disubstituted pyrrolidine derivatives by nucleophilic addition to bicyclic N-acyliminium ion

5-Alkoxy-pyrroloxazolidin-3-ones 1 were stereoselectively prepared from (S)-pyroglutamic acid. Treatment of 1 with a Lewis acid generated in situ the N-acyliminium 2, which was trapped by various π-nuclcophiles leading selectively to trans pyrrolidine derivatives 3.

Kinetic resolution of secondary alcohols using proline-derived bicyclic iminium salts

The proline-derived bicyclic iminium salt 3 can be used to bring about kinetic resolution in its reaction with salts of secondary alcohols to give the corresponding methyl sulfides. Reaction proceeds most efficiently with sodium 1-phenylethoxide in toluene at RT where either 3 or the benzyl salt 14 give e.e.s of 21-25% and changing the heteroatoms present in the sails, the metal cation used and the solvent and temperature all give similar or lower selectivity.

Palladium-Catalyzed Double and Single Carbonylations of β-Amino Alcohols. Selective Synthesis of Morpholine-2,3-diones and Oxazolidin-2-ones and Applications for Synthesis of α-Oxo Carboxylic Acids

Catalytic cross double carbonylation of secondary amines and alcohols proceeds in the presence of [PdCl2(MeCN)2] and CuI under carbon monoxide (80 atm) and oxygen (5 atm). Catalytic intramolecular double carbonylation of β-amino alcohols gives morpholine-2,3-diones, which are excellent protecting compounds of amino alcohols and important precursors for biologically active nitrogen compounds. In contrast, catalytic single carbonylation of β-amino alcohols under a mixture (1 : 1) of carbon monoxide and oxygen (1.0 atm) proceeds to give oxazolidin-2-ones selectively. The reaction can be explained by assuming a mechanism which includes intramolecular nucleophilic attack of the hydroxy group of (hydroxyethyl)aminocarbonyl ligands on the CO ligand of the carbamoylpalladium(II) complexes, followed by reductive elimination to give morpholine-2,3-diones. In contrast, direct nucleophilic attack of the hydroxy group to the carbamoyl group affords oxazolidin-2-ones. As a common intermediate for the double and single carbonylations, carbamoylpalladium(II) complex has been isolated by the reaction of [PdCl2(PMe3)2] with β-amino alcohol under CO. The present double carbonylation of amino alcohols provides a novel and convenient method for synthesis of α-oxo carboxylic acids. Thus, the morpholine-2,3-diones obtained undergo reaction with Grignard reagents chemoselectively at the ester positions to give 2-substituted 2-hydroxymorpholin-3-ones, which undergo acid hydrolysis to give α-oxo carboxylic acids.