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Chemical Structure| 504-78-9 Chemical Structure| 504-78-9

Structure of Thiazolidine
CAS No.: 504-78-9

Chemical Structure| 504-78-9

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Product Details of [ 504-78-9 ]

CAS No. :504-78-9
Formula : C3H7NS
M.W : 89.16
SMILES Code : S1CNCC1
MDL No. :MFCD00005211
InChI Key :OGYGFUAIIOPWQD-UHFFFAOYSA-N
Pubchem ID :10444

Safety of [ 504-78-9 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225
Precautionary Statements:P210-P403+P235
Class:3
UN#:1993
Packing Group:

Application In Synthesis of [ 504-78-9 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 504-78-9 ]

[ 504-78-9 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 504-78-9 ]
  • [ 24424-99-5 ]
  • [ 148312-55-4 ]
YieldReaction ConditionsOperation in experiment
86.2% In 1,4-dioxane; water; a. N-tert-butoxycarbonyl-thiazolidine. 24 g (0.11 mole) of di-tert-butyl dicarbonate dissolved in 50 ml of dioxane are added dropwise to a solution of 8.9 g (0.1 mole) of thiazolidine in 50 ml of dioxane and 50 ml of water, while maintaining the pH between 10 and 10.5 by addition of soda lye. The mixture is stirred at room temperature for 6 hours. The formed salts are filtered off and the organic solvent is evaporated under reduced pressure. The aqueous residue is extracted with dichloromethane (2*50 ml), the organic phase is decanted, dried over sodium sulfate and the solvent is evaporated off. The residue is purified by distillation under reduced pressure. 16.3 g of N-tert-butoxycarbonyl-thiazolidine are obtained. Yield: 86.2%. B.P.: 56-57 C./6.7 mbars.
  • 2
  • [ 504-78-9 ]
  • [ 218609-00-8 ]
  • [1-(4-fluoro-benzyl)-3-oxo-3-thiazolidin-3-yl-propyl]-carbamic acid <i>tert</i>-butyl ester [ No CAS ]
  • 3
  • [ 504-78-9 ]
  • [ 218608-96-9 ]
  • [1-(4-chloro-benzyl)-3-oxo-3-thiazolidin-3-yl-propyl]-carbamic acid <i>tert</i>-butyl ester [ No CAS ]
  • 4
  • [ 504-78-9 ]
  • [ 59969-65-2 ]
  • (2S,3R)-3-benzyloxycarbonylamino-2-hydroxy-4-phenylbutanoic acid thiazolidide [ No CAS ]
  • 5
  • [ 504-78-9 ]
  • [ 27486-87-9 ]
  • [ 311343-09-6 ]
YieldReaction ConditionsOperation in experiment
80% for 12h; The coupling reaction of 7 (2 mmol) with thiazolidine is carried out according to method A described in the first synthetic route (example 1). After returning to ambient temperature, stirring is continued for 12 h. The reaction medium is then diluted with 50 ml of AcOEt, then washed (water, 70 ml; ice-cold saturated sodium bicarbonate, 50 ml; water, 2×50 ml), dried over sodium sulfate and evaporated to dryness under vacuum. The colorless foam obtained is subsequently purified by flash chromatography on a silica gel column (eluent: AcOEt/petroleum ether 30%). 18 is isolated in the form of a colorless gum with a yield of 80%. Rf (AcOEt/petroleum ether, 8/2): 0.40. Crystallizes from MeOH in colorless needles. M.p.=197-198 C. [alpha]D20=+0.86 (c 1.16, CHCl3) [0268] 1H NMR (CDCl3) delta ppm (isomeric mixture, 5.2/4.8: 1.95 (s, 3H, NCOCH3), 2.48-2.66 (m, 2H, CH2 cys), 2.88-3.02 (m, 2H, H5, H5' Thz), 3.24-3.34, 3.64-3.75, 3.77-3.86 (3m, 2H, H4, H4' Thz), 3.96, 4.41 and 4.45, 4.54 (2×2d, J=2×8.8 and 2×10.3 Hz, 2H, H2, H2' Thz), 4.60-4.69 (m, 1H, alpha H cys), 6.05-6.15 (m, 1H, NH cys), 7.18-7.34, 7.36-7.44 (2m, 15H, aromatic H). MS: (FAB+/G-T) m/z 953 (2M+H)+, 477 (M+H)+. Analysis: C27H28N2O2S2 (476) [TABLE-US-00051] Calc. %: C 68.07 H 5.88 N 5.88 Found %: 67.97 5.84 5.89
  • 6
  • [ 504-78-9 ]
  • [ 84348-37-8 ]
  • [ 401564-36-1 ]
YieldReaction ConditionsOperation in experiment
86% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In ethyl acetate; at 2 - 7℃; for 2h;Large scale; To (2S)-1-tert-butoxycarbonyl-4-oxopyrrolidine-2-carboxylic acid (Compound 8a) (60.0 kg),thiazolidine (30.3 kg) and N,N-diisopropylethylamine ( 118kg) in ethyl acetate and propylphosphonic anhydride (595kg) (cyclic trimer) was added 28w% at 2 -7 C in ethyl acetate (446kg) was added and the reaction mixture was 2 -4 C stirred for 2 hours. To this reaction mixture was added 15w% aqueous citric acid (600kg) for distribution, and the aqueous layer with ethyl acetate (271kg) extract. The ethyl acetate layer obtained was mixed, and sequentially washed with 10w% aqueous solution of diammoniumphosphate (600kg) and water (300kg). The ethyl acetate layer was concentrated to a residual volume 300L, n-heptane (739kg) at 23 -25 C added, and the mixture wasstirred at 23 -25 C 1 hour and stirred at 1 -5 C. The precipitated crystals were collected by filtration, with n-heptane (164 kg) were washed and driedunder reduced pressure to yield 3-[(2S)-1-tert-butoxycarbonyl-4-oxopyrrolidin-2-ylcarbonyl]thiazolidine (compound 9a) (67.8 kg, yield 86 %)
86% (2S) -1-t-butoxycarbonyl-4-oxopyrrolidine-2-carboxylic acid (Compound 3a)(250.0 kg), N, N-diisopropylethylamine (DIPEA) (141 kg) in ethyl acetate (2242.5 kg) was added with pivaloyl chloride (131.5 kg) at 10 C. or lower, and the reaction mixture was added. The mixture was stirred at 10 C. or lower for 30 minutes.After thiazolidine (97.2 kg) was added to the reaction mixture at 10 C. or lower,The reaction mixture was stirred at 0-10 C. for 1 hour.To this reaction mixture, water (500.0 kg) was added for liquid separation,Ethyl acetate layer was prepared with diammonium hydrogen phosphate aqueous solution (prepared from 144.0 kg ammonium hydrogen phosphate and water (750.0 kg)) and saline (prepared from salt (75.0 kg) and water (425.0 kg)). Washed sequentially.After concentrating the ethyl acetate layer to a residual amount of 1250 L,2-Propanol (976.3 kg) was added and concentrated again.After the remaining amount was 1000 L, n-heptane (1368 kg) was added at 40 to 45 C., and the mixture was stirred at -5 C. or lower for 1 hour.The precipitated crystals were collected by filtration and washed with n-heptane (684.0 kg).2-Propanol (429.6 kg) was added to the obtained crystals, n-heptane (1521.9 kg) was added at 40 to 45 C., and the mixture was stirred at -5 C. or lower for 1 hour.The precipitated crystals are collected by filtration, washed with n-heptane (769.8 kg), and then dried under reduced pressure.3-[(2S) -1-t-butoxycarbonyl-4-oxopyrrolidin-2-ylcarbonyl] thiazolidine283.1 kg of (Compound 2a) was obtained.(Yield 86%)
81.7% A solution of DCC (107.8 g) in toluene (300 mL) was added to a solution of 1-(tert-butoxycarbonyl)-4-oxo-L-proline (prepared according to the process of Example 2; 100 g) in toluene (900 mL) at -5C to - 10C, and the reaction mixture was stirred for 30 minutes at the same temperature. Dimethylaminopyridine (1 g) and thiazolidine (46.7 g) were slowly added to the reaction mixture at a temperature of about -6C to -2C over a period of about 15 to 20 minutes. The reaction mixture was allowed to warm to a temperature of 0C to 5C, and stirred at the same temperature for 60 minutes. When the reaction was complete, the reaction mixture was quenched with deionized water (20 mL), and stirred at 20C to 25C for 30 minutes. The resulting mixture was filtered through a Hyflo bed. The filtrate was washed with aqueous sodium bicarbonate solution (50 g sodium carbonate in 500 mL deionized water). The organic layer was separated and washed with an aqueous solution of sodium chloride (50 g sodium chloride in 500 mL deionized water). Activated carbon (10 g) was added to the organic layer, and the reaction mixture was stirred at 25C to 30C for 30 minutes. The reaction mixture was filtered through a Hyflo bed, and concentrated at a temperature of 50C under reduced pressure. The residue obtained was dissolved in ethyl acetate (200 mL) at 50C to 55C. Hexanes (800 mL) were added at 50C to 55C over a period of 1 to 2 hours. The reaction mixture was further cooled to a temperature of 0C to 5C, and stirred at the same temperature for 3 hours. The reaction mixture was filtered to obtain a solid. The solid was washed with a pre-cooled (0C to 5C) mixture of ethyl acetate (80 mL) and hexanes (320 mL), and dried at a temperature of 40C to 45C under reduced pressure to obtain tert-Butyl (2S)-4-oxo-2-(1.3-thiazolidin-3- ylcarbonyl)pyrrolidine-1-carboxylate. Yield: 81.7%
81.7% With dmap; dicyclohexyl-carbodiimide; In toluene; at -6 - 5℃; for 1.33333h; A solution of DCC (107.8 g) in toluene (300 mL) was added to a solution of 1- (tert-butoxycarbonyl)-4-oxo-L-proline (Formula V, prepared according to Example 2; 100 g) in toluene (900 mL) at -10C to -5C. The reaction mixture was stirred for 30 minutesat -10C to -5C. 4-Dimethylaminopyridine (1 g) and thiazolidine (46.7 g) were slowly added to the reaction mixture at -6C to -2C over a period of 15 minutes to 20 minutes. The reaction mixture was allowed to warm to 0C to 5C, then stirred at the same temperature for 60 minutes. When the reaction was complete, the reaction mixture was quenched with deionized water (20 mL), then stirred at 20C to 25C for 30 minutes. Theresulting mixture was filtered through a Hyflo bed. The filtrate was washed with an aqueous sodium bicarbonate solution (50 g sodium carbonate in 500 mL deionized water). The organic layer was separated, then washed with an aqueous solution of sodium chloride (50 g sodium chloride in 500 mL deionized water). Activated carbon (10 g) was added to the organic layer, then the reaction mixture was stirred at 25C to 30C for 30 minutes.The reaction mixture was filtered through a Hyflo bed, then concentrated at 50C under reduced pressure. The residue obtained was dissolved in ethyl acetate (200 mL) at 50C to 55C. Hexanes (800 mL) were added at 50C to 55C over a period of one hour to 2 hours. The reaction mixture was further cooled to 0C to 5C, then stirred at the same temperature for 3 hours. The reaction mixture was filtered to obtain a solid. The solidwas washed with a precooled (0C to 5C) mixture of ethyl acetate (80 mL) and hexanes (320 mL), then dried at 40C to 45C under reduced pressure to obtain tert-butyl (2S)-4- oxo-2-( 1,3 -thiazolidin-3 -ylcarbonyl)pyrrolidine- 1 -carboxylate.Yield: 81.7% HPLC Purity: 98.97 %
50 kg 6) Add 500 kg of toluene to a dry 2000 L reactor and add N-Boc-4-oxo-L-proline in batches.50 kg (molar amount: 229.23, molar amount: 218 mol), after stirring and dissolved, the system was cooled to below 0 C. Slowly add EDC hydrochloric acidSalt 50kg (molar amount 191.7, molar amount 261mol), and kept below 0 C for 3h;7), control system temperature below 0 C, dropwise addition of 23.4 kg of tetrahydrothiazole (molar amount 89.16, molar amount 260 mol) andA mixture of 533 g of 4-dimethylaminopyridine (molar amount 122.17, mole number 4.36) was added in about 1 h. Incubate for 1 h below 0 C;The end of the reaction of controlling N-Boc-4-oxo-L-proline in HPLC can be post-treated;8), post-treatment: the reaction solution is centrifuged, the filter cake is beaten with toluene, the organic phase is combined, 500 kg of water is added to stir, hydrochloric acid is added.Adjust the pH to about 3. The aqueous phase is separated, and the organic phase is washed with water and saturated brine, respectively, and dried and filtered;9), the organic phase is concentrated under reduced pressure at 50 C to obtain a solid and dried with an oil pump;10), the solid was recrystallized from a mixed solvent of ethyl acetate and n-hexane (ethyl acetate: n-hexane = 1:4), 250 kg.The temperature is raised from 55 C to 60 C, stirred and dissolved, and the temperature is lowered by 0 C. Centrifugation and drying gave a solid 50 kg. Yield: 76.3%. HPLC>99%, single miscellaneous <0.3%.

  • 7
  • [ 504-78-9 ]
  • [ 102195-80-2 ]
  • [ 401564-36-1 ]
YieldReaction ConditionsOperation in experiment
90% With acetic acid; In methanol; at 0 - 30℃; for 2.5h;Large scale; Add 1500 Kg of methanol to the reaction kettle.250Kg compound 3-1, acetic acid 6.4Kg,Then, the temperature was lowered to 0 to 5 C, and then 96 kg of tetrahydrothiazole was added dropwise to the reaction vessel at an internal temperature of not more than 10 C.After the completion of the dropwise addition, the reaction was kept at 0 to 5 C for 2 h, and then raised to 30 C for 0.5 h.After the reaction is completed, the mixture is concentrated under reduced pressure until solvent-free evaporation.Add 1500 Kg of dichloromethane, 300 Kg of saturated sodium bicarbonate solution to the reaction kettle, and stir for 30 minutes.After standing for 30 minutes, the layers were separated, and the organic layer was washed twice with 150 Kg of brine.The organic phase was concentrated under reduced pressure to give a pale yellow solid.The crude product was then dissolved in 280 kg of ethyl acetate.Heat to 50 ~ 55 C, dissolve, add 1120Kg petroleum ether to the reaction kettle, add dropwise,Slowly cool to 0 ~ 5 C, and crystallization at 0 ~ 5 C for 30 minutes.After centrifugation, the solid was washed with a petroleum ether: ethyl acetate (4:1) mixed solution of 100 Kg.Drying at 45 to 50 C gives 278 Kg of compound 4-1.The yield was 90%.
 

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Related Parent Nucleus of
[ 504-78-9 ]

Thiazolidines

Chemical Structure| 14446-47-0

A252861 [14446-47-0]

Thiazolidine hydrochloride

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