114676-61-8

Basic information

• Product Name: (2S,4R)-4-hydroxy-2-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester
• Synonyms: (2S,4R)-4-hydroxy-2-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester;tert-butyl (2s,4r)-4-hydroxy-2-methylpyrrolidine-1-carboxylate;(2S,4R)-tert-butyl 4-hydroxy-2-methylpyrrolidine-1-carboxylate
• CAS NO: 114676-61-8
• Molecular Formula: C₁₀H₁₉NO₃
• Molecular Weight: 201.26276
• Mol File: 114676-61-8.mol
• Article Data: 5

Chemical Properties

• Melting Point: 75-78 °C
• Boiling Point: 282.5±33.0 °C(Predicted)
• Appearance: /
• Density: 1.094±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• PKA: 14.75±0.40(Predicted)
• CAS DataBase Reference: (2S,4R)-4-hydroxy-2-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: (2S,4R)-4-hydroxy-2-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester(114676-61-8)
• EPA Substance Registry System: (2S,4R)-4-hydroxy-2-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester(114676-61-8)

Safety Data

• Hazardous Substances Data: 114676-61-8(Hazardous Substances Data)

Usage

General Description

"(2S,4R)-4-hydroxy-2-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester" is a complex organic chemical compound. It consists primarily of pyrrolidine as the basic structure which is a type of organic compound that comes under the category of cyclic amines. Within this compound, "2S, 4R" refers to stereochemical configuration of the molecule. The “4-hydroxy” refers to the presence of a hydroxyl group (-OH) in the molecule, specifically at the 4th position. The "2-methyl" means a methyl group (-CH3) is attached at the 2nd position. "1-carboxylic acid tert-butyl ester" signifies that the compound contains a carboxylic acid functionally attached at the 1st position, which is further esterified with tert-butyl group. These chemical features determine the compound's reactivity, solubility and overall chemical behavior. The specific properties and uses depend on the context in which this chemical is being synthesized or employed, often in specialized chemical, pharmaceutical or academic research.

Synthetic route

tert-butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-methylpyrrolidine-1-carboxylate (213699-41-3) → tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃;	99%
With tetrabutyl ammonium fluoride In tetrahydrofuran for 2.5h; Yield given;
With tetrabutyl ammonium fluoride In tetrahydrofuran

(R)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate (109431-87-0) + dimethyl sulfate (77-78-1) → (2R,4R)-tert-butyl 4-hydroxy-2-methylpyrrolidine-1-carboxylate (114676-93-6) + tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8)

Conditions	Yield
With N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium In tetrahydrofuran 1.) -78 to -46 deg C, 2 h, 2.) -78 deg C; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium In tetrahydrofuran 1.) -78 to -46 deg C, 2 h, 2.) -78 deg C; Yield given. Yields of byproduct given;

di-tert-butyl dicarbonate (24424-99-5) → tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8)

Conditions	Yield
Multi-step reaction with 6 steps 1: 90 percent / triethylamine / CH2Cl2 / 12 h 2: 99 percent / imidazole / dimethylformamide / 1.5 h / Ambient temperature 3: 93 percent / lithium borohydride / tetrahydrofuran / 16 h 4: 94 percent / triethylamine / CH2Cl2 / 15 h 5: lithium triethylborohydride / tetrahydrofuran / 2 h 6: tetra-n-butylammonium fluoride / tetrahydrofuran / 2.5 h View Scheme

(2R,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (114676-69-6) → tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8)

Conditions	Yield
Multi-step reaction with 5 steps 1: 99 percent / imidazole / dimethylformamide / 1.5 h / Ambient temperature 2: 93 percent / lithium borohydride / tetrahydrofuran / 16 h 3: 94 percent / triethylamine / CH2Cl2 / 15 h 4: lithium triethylborohydride / tetrahydrofuran / 2 h 5: tetra-n-butylammonium fluoride / tetrahydrofuran / 2.5 h View Scheme

(2R,4R)-4-hydroxy-2-methoxycarbonylpyrrolidine hydrochloride (114676-59-4) → tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8)

Conditions	Yield
Multi-step reaction with 6 steps 1: 90 percent / triethylamine / CH2Cl2 / 12 h 2: 99 percent / imidazole / dimethylformamide / 1.5 h / Ambient temperature 3: 93 percent / lithium borohydride / tetrahydrofuran / 16 h 4: 94 percent / triethylamine / CH2Cl2 / 15 h 5: lithium triethylborohydride / tetrahydrofuran / 2 h 6: tetra-n-butylammonium fluoride / tetrahydrofuran / 2.5 h View Scheme

(2R,4R)-tert-butyl 4-((tert-butyldimethylsilyl)oxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylate (114676-58-3) → tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 94 percent / triethylamine / CH2Cl2 / 15 h 2: lithium triethylborohydride / tetrahydrofuran / 2 h 3: tetra-n-butylammonium fluoride / tetrahydrofuran / 2.5 h View Scheme
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 0 °C 2: sodium triethylborohydride / tetrahydrofuran / 2 h / 5 - 20 °C 3: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C View Scheme

1-(2-chloro-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl)ethan-1-one + tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) → tert-butyl (2S,4R)-4-((6-acetyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-yl)oxy)-2-methylpyrrolidine-1-carboxylate

Conditions	Yield
Stage #1: tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate With sodium hydride In tetrahydrofuran; mineral oil at 10 - 41℃; for 0.416667h; Stage #2: 1-(2-chloro-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl)ethan-1-one In tetrahydrofuran; mineral oil at 40℃; Temperature;	99%

toluene-4-sulfonic acid (104-15-4) + tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) → (3R,5S)-5-methylpyrrolidin-3-ol 4-methylbenzenesulfonate

Conditions	Yield
In water; isopropyl alcohol at 62℃;	93%

tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) + methyl iodide (74-88-4) → tert-butyl (2S,4R)-4-methoxy-2-methylpyrrolidine-1-carboxylate

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 1h;	92%

5-bromo-2-fluoropyridine (766-11-0) + tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) → tert-butyl (2S,4R)-4-[(5-bromo-2-pyridyl)oxy]-2-methylpyrrolidine-1-carboxylate

Conditions	Yield
With sodium hydride In tetrahydrofuran at 90℃; for 2h;	86%

formic acid (64-18-6) + tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) → (2S,4S)-4-Formyloxy-2-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester (477293-59-7)

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; Mitsunobu esterification;	83%

1-(2-chloro-5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)ethan-1-one + tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) → tert-butyl (2S,4R)-4-((6-acetyl-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-2-yl)oxy)-2-methylpyrrolidine-1-carboxylate

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at 50℃; for 4.5h;	47%

ethyl 2-chloroimidazo[1,2-a]pyrimidine-3-carboxylate (1431554-41-4) + tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) → ethyl 2-(((3R,5S)-1-(tert-butoxycarbonyl)-5-methylpyrrolidin-3-yl)oxy)imidazo[1,2-a]pyrimidine-3-carboxylate

Conditions	Yield
With sodium hydride In tetrahydrofuran at 90℃; for 12h;	40%

1-(3-bromo-5,7-dihydropyrrolo[3,4-b]pyridin-6-yl)ethanone + tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) → tert-butyl (2S,4R)-4-[(6-acetyl-5,7-dihydropyrrolo[3,4-b]pyridin-3-yl)oxy]-2-methylpyrrolidine-1-carboxylate

Conditions	Yield
With methanesulfonato(2-di-t-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-tri-i-propylbiphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II); caesium carbonate In toluene at 75℃; for 72h;	24%

1-(6-chloro-1,3-dihydropyrrolo[3,4-c]pyridin-2-yl)ethanone + tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) → tert-butyl (2S,4R)-4-[(2-acetyl-1,3-dihydropyrrolo[3,4-c]pyridin-6-yl)oxy]-2-methyl-pyrrolidine-1-carboxylate

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran at 45℃; for 5h;	22%

7-chloroimidazo[1,2-c]pyrimidine (55662-71-0) + tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) → tert-butyl (2S,4R)-4-(imidazo[1,2-c]pyrimidin-7-yloxy)-2-methylpyrrolidine-1-carboxylate

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 110℃; for 15h; Inert atmosphere;	21%

methanesulfonyl chloride (124-63-0) + tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) → (2S,4R)-4-Methanesulfonyloxy-2-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester (114677-04-2)

Conditions	Yield
With triethylamine In dichloromethane for 14h;	16.1 g
With triethylamine

tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) + C24H31F3O6S (289710-47-0) → C33H49NO6 (477293-54-2)

Conditions	Yield
With sodium hydride In N,N-dimethyl acetamide at 0℃;

tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) → tert-Butyl (2S,4S)-4-hydroxy-2-methyl-pyrrolidine-1-carboxylate (477293-60-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 83 percent / Ph3P; DEAD / tetrahydrofuran / 20 °C 2: 90 percent / aq. NaOH / tetrahydrofuran / 20 °C View Scheme

tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) → (2S,4R)-4-Acetylsulfanyl-2-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester (477293-61-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 83 percent / Ph3P; DEAD / tetrahydrofuran / 20 °C 2: 90 percent / aq. NaOH / tetrahydrofuran / 20 °C 3: 66 percent / Ph3P; DEAD / tetrahydrofuran / 20 °C View Scheme

tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) → C28H41NO3S (477293-63-3)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: 83 percent / Ph3P; DEAD / tetrahydrofuran / 20 °C 2.1: 90 percent / aq. NaOH / tetrahydrofuran / 20 °C 3.1: 66 percent / Ph3P; DEAD / tetrahydrofuran / 20 °C 4.1: NaOMe / dimethylformamide / 0 °C 4.2: 47 percent / dimethylformamide / 20 °C 5.1: 81 percent / TFA / CH2Cl2 / 20 °C View Scheme

tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) → C32H43NO3S

Conditions

Yield

Multi-step reaction with 7 steps 1.1: 83 percent / Ph3P; DEAD / tetrahydrofuran / 20 °C 2.1: 90 percent / aq. NaOH / tetrahydrofuran / 20 °C 3.1: 66 percent / Ph3P; DEAD / tetrahydrofuran / 20 °C 4.1: NaOMe / dimethylformamide / 0 °C 4.2: 47 percent / dimethylformamide / 20 °C 5.1: 81 percent / TFA / CH2Cl2 / 20 °C 6.1: 21 percent / K2CO3; KI / acetonitrile / 20 °C 7.1: 52 percent / Pd(PPh3)4; morpholine / tetrahydrofuran / 20 °C View Scheme

tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) → C35H47NO3S (477293-64-4)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: 83 percent / Ph3P; DEAD / tetrahydrofuran / 20 °C 2.1: 90 percent / aq. NaOH / tetrahydrofuran / 20 °C 3.1: 66 percent / Ph3P; DEAD / tetrahydrofuran / 20 °C 4.1: NaOMe / dimethylformamide / 0 °C 4.2: 47 percent / dimethylformamide / 20 °C 5.1: 81 percent / TFA / CH2Cl2 / 20 °C 6.1: 21 percent / K2CO3; KI / acetonitrile / 20 °C View Scheme

tert-butyl (2S,4R)-4-hydroxyl-2-methylpyrrolidine-1-carboxylate (114676-61-8) → C33H49NO5S (477293-62-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 83 percent / Ph3P; DEAD / tetrahydrofuran / 20 °C 2.1: 90 percent / aq. NaOH / tetrahydrofuran / 20 °C 3.1: 66 percent / Ph3P; DEAD / tetrahydrofuran / 20 °C 4.1: NaOMe / dimethylformamide / 0 °C 4.2: 47 percent / dimethylformamide / 20 °C View Scheme

Upstream product

• 213699-41-3 tert-butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-methylpyrrolidine-1-carboxylate 
• 109431-87-0 (R)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate 
• 77-78-1 dimethyl sulfate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 114676-69-6 (2R,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate 
• 114676-59-4 (2R,4R)-4-hydroxy-2-methoxycarbonylpyrrolidine hydrochloride 
• 114676-58-3 (2R,4R)-tert-butyl 4-((tert-butyldimethylsilyl)oxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylate 
• 114760-51-9 (2R,4R)-1-(tert-butixycarbonyl)-4-<(tert-butyldimethylsilyl)oxy>-2-carbomethoxypyrrolidine 
• 114676-60-7 (2R,4R)-4-(tert-Butyl-dimethyl-silanyloxy)-2-methanesulfonyloxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 2584-71-6 cis-hydroxy-D-proline 
• 114676-91-4 1-tert-butyl 2-methyl (2S,4R)-4-{[tert-butyl(dimethyl)silyl]oxy}pyrrolidine-1,2-dicarboxylate 
• 114676-92-5 (2S,4R)-1-(tert-butoxycarbonyl)-4-<(tert-butyldimethylsilyl)oxy>-2-<<(methylsulfonyl)oxy>methyl>pyrrolidine 

Downstream Products

• 477293-60-0 (2S,4S)-4-hydroxy-2-methylpyrrolidine-1-carboxylic acid tert-butyl ester 
• 477293-64-4 C₃₅H₄₇NO₃S 
• 152673-32-0 (2S,4S)-4-amino-2-methylpyrrolidine-1-carboxylic acid tert-butyl ester 
• 121332-92-1 7-((2S,4S)-4-Acetylamino-2-methyl-pyrrolidin-1-yl)-6-fluoro-1-(4-fluoro-phenyl)-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid ethyl ester 
• 114676-86-7 (2'S,4'S)-7-(4'-amino-2'-methylpyrrolidinyl)-1-(p-fluorophenyl)-1,4-dihydro-6-fluoro-4-oxoquinoline-3-carboxylic acid hydrochloride 
• 114676-82-3 (2'S,4'S)-7-(4'-amino-2'-methylpyrrolidinyl)-1-(2,4-difluorophenyl)-1,4-dihydro-6-fluoro-4-oxoquinoline-3-carboxylic acid hydrochloride 
• 114676-87-8 (2'S,4'S)-7-(4'-amino-2'-methylpyrrolidinyl)-1,4-dihydro-6-fluoro-1-(p-fluorophenyl)-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride 
• 114676-84-5 (2'S,4'S)-7-(4'-amino-2'-methylpyrrolidinyl)-1-(2,4-difluorophenyl)-1,4-dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid 
• 114677-01-9 (2'S,4'S)-7-(4'-acetamido-2'-methylpyrrolidinyl)-1-(2,4-difluorophenyl)-1,4-dihydro-6-fluoro-4-oxoquinoline-3-carboxylic acid ethyl ester 
• 121332-89-6 7-((2S,4S)-4-Acetylamino-2-methyl-pyrrolidin-1-yl)-1-(2,4-difluoro-phenyl)-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid ethyl ester 
• 1108234-23-6 (3R,5S)-5-methylpyrrolidin-3-ol 
• 1027775-28-5 tert-butyl (2R)-2-methyl-4-oxopyrrolidine-1-carboxylate 

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