Heterocyclic Building Blocks-Oxazolidine

With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.90319-52-1,(R)-4-Phenyloxazolidin-2-one,as a common compound, the synthetic route is as follows.

To a solution of bromoethynylbenzene (1.4 g, 8.0 mmol) in 24 mL of anhydrous toluene in a reaction vial were added methyl phenylcarbamate (1.5 g, 9.6 mmol), K3PO4 (3.4 g, 16 mmol), copper sulfate-pentahydrate (400 mg, 16 mmol), and 1,10-phenanthroline (577 mg, 3.2 mmol). The reaction mixtures was capped under an argon atmosphere, and heated in an oil bath at 80 ?C for 15 h. The progress of the reaction was monitored using TLC analysis. Upon completion, the reaction mixture was allowed to cool to room temperature, and diluted with 15 mL of ethyl acetate. The mixture was filtered through a pad of celite, and the filtrate was concentrated in vacuo. The crude residue was purified by column chromatography with eluent of Hexane/ ethyl acetate = 19/1 to give 1.6 g of 1 in 80 percent yield as a yellow oil. 1H NMR (400 MHz, CDCl3) delta 7.55 (dd, J = 1.2, 8.6 Hz, 2H), 7.45-7.40 (m, 4H), 7.33-7.28 (m, 4H), 3.92 (s, 3H). 13C NMR. (100 MHz, CDCl3) delta 154.9, 139.7, 131.5, 129.1, 128.4, 128.0, 127.2, 124.8, 123.0, 83.0, 70.3, 54.5.#10;, 90319-52-1

As the paragraph descriping shows that 90319-52-1 is playing an increasingly important role.

Reference£º
Article; Sato, Akihiro H.; Ohashi, Kazuhiro; Iwasawa, Tetsuo; Tetrahedron Letters; vol. 54; 10; (2013); p. 1309 – 1311;,
Oxazolidine – Wikipedia
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With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.99395-88-7,(S)-4-Phenyloxazolidin-2-one,as a common compound, the synthetic route is as follows.

(2) nitrogen protection, will (S)-4 – phenyl -2 oxazolidone (2.5 kg, 15.3 muM) is added to the in tetrahydrofuran (20L), stirring and dissolving, control the temperature of the reaction solution in the 15 – 25 C, batch repeatedly added 60% NaH (625g, 15.6 muM). Feeding after completely, adds by drops differently pivaloyl chloride (1.9 kg, 15.8 muM), to maintain the temperature of the reaction solution is lower than the 30 C. Dropping after completely, thermal insulation reaction 30min. TLC monitoring raw material the reaction is complete. The reaction liquid slowly poured into saturated NH4Cl (40L) in aqueous solution quenching, and the room temperature stirring reaction 2h, layered, separating the organic phase, the aqueous layer and then the extraction of ethyl acetate (15L ¡Á 2), the combined organic layer, steaming and to dry. In the concentrate is added to the petroleum ether (4L), full mixing, filtering, results in the type (I – S) compound of formula 3.41 kg. The yield is 90%.

99395-88-7, As the paragraph descriping shows that 99395-88-7 is playing an increasingly important role.

Reference£º
Patent; Borui Bio-pharmaceutical (Suzhou) Co., Ltd.; Yuan Jiandong; Liu Wei; Ma Shimin; (29 pag.)CN104058990; (2017); B;,
Oxazolidine – Wikipedia
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147959-19-1, The molecularity of an elementary reaction is the number of molecules that collide during that step in the mechanism. If there is only a single reactant molecule in an elementary reaction, that step is designated as unimolecular. 147959-19-1, name is (S)-tert-Butyl 2,2-dimethyl-4-(2-oxoethyl)oxazolidine-3-carboxylate. A new synthetic method of this compound is introduced below.

With key building block 6 in hand, its nitroaldol (Henry) reaction with nitromethane was examined (Table 1). LiAlH418- TBAF19- as well as t-BuOK20-catalyzed Henry reactions led to nitro alcohols 12 and 13 with low diastereoselectivity, reflecting that the existing stereogenic center is too far away from the newly created one to exert appreciable asymmetric induction (Table 1, entries 1-3).21 An obvious way of resolving this problem was the introduction of additional chiral information, i.e. application of a chiral catalyst. In fact double stereodifferentiation using Shibasaki’s well established heterobimetallic (,S)-BINOL catalyst 1422 (5 mol%, THF, -40 C, 3 d) led to 12 with high diastereoselectivity albeit in low yield (Table 1, entry 4).Recently, other highly efficient chiral catalysts for asymmetric Henry reactions have been developed. Thus, Corey23 and Maruoka24 have utilized chiral quaternary ammonium fluorides as catalysts while Trost25 has presented a dinuclear zinc catalyst. Salen-cobalt(II) complexes have been used by Yamada whereas J¡ãrgensen and Evans have introduced bis(oxazoline)-coprhoer(II) complexes. The latter seemed to be the catalysts of choice, at least for aliphatic aldehydes, with respect to attainable yields and degree of stereoselectivity. EPO Table 1. Diastereoselective Henry Reaction of Aldehyde 6 with Nitromethaneyield ratio0 entry catalyst conditions(%)a 12:131 LiAlH4 THF, rt 53 56:442 TBAF THF, rt 33 43:573 r-BuOK t- 72 23:77BuOH/THF,00C4 14 THF, -40 C 45 98:25 {Cu[(+> EtOH, rt 87 92:815]} (OAc)26 (CuK-)- EtOH, rt 85 9:9115]}(OAc)27 {Cu[(+> EtOH, rt 94 97:316]}(OAc)28 (Cu[(-)- EtOH, rt 91 8:9216I)(OAc)2a isolated yield b determined by HPLC analysis of crude reaction mixtures EPO Indeed application of Evans’ bis(oxazoline) copper(II) acetate-based catalysts {Cu[(+)- 15]}(OAc)2 and in particular {Cu[(+)-16]}(OAc)2 (5 mol%, EtOH, rt, 5 d) gave the desired nitro alcohol 12 both with high diastereoselectivity and in high yield (Table 1 , entries 5 and 7). Finally, to obtain selectively diastereomer 13, aldehyde 6 was reacted with nitromethane in the presence of the enantiomeric catalysts {Cu[(-)-15]}(OAc)2 and {Cu[(-)-16]} (OAc)2 respectively. In these cases slightly lower stereoselectivities and yields were observed reflecting a mismatched pairing (Table 1, entries 6 and 8).

There are, however, a few established termolecular elementary reactions. The reaction of nitric oxide with oxygen appears to involve termolecular steps. you can also browse my other articles about147959-19-1

Reference£º
Patent; LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN; WO2006/94770; (2006); A2;,
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99395-88-7, A balanced equation for a chemical reaction indicates what is reacting and what is produced, but it reveals nothing about how the reaction actually takes place. The reaction mechanism is the process, or pathway, by which a reaction occurs.3663-80-7. An updated downstream synthesis route of 3663-80-7 as follows.

Example 21 (S,E)-3-(pent-2-enoyl)-4-phenyl oxazolidin-2-one The 4S-phenyl-2-oxazolidinone (5.6 g, 34.4 mmol) was placed in a three-necked flask, after it was purged with nitrogen, tetrahydrofuran was added and it was cooled to -78 C., then n-butyl lithium (1.6M, 22 ml, 35.4 mmol) was added dropwise, and the reaction was carried out for 30 minutes. After that, a solution of 2-pentenoyl chloride (4.2 g, 35.5 mmol) in tetrahydrofuran was added dropwise, and the reaction was continued for 30 minutes, then it was slowly raised to 0 C., the reaction was continued for 2 hours and quenched with saturated ammonium chloride solution. The reaction solution was then concentrated to remove tetrahydrofuran and extracted with ethyl acetate 3 times, then the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and recrystallized with petroleum ether and ethyl acetate to give a white solid 8 g, yield: 95%. 1HNMR (300 MHz, CDCl3): delta 7.3-7.4 (5H, m), 7.1-7.2 (1H, m), 6.9-7.1 (1H, m), 5.5 (1H, dd, J=4.2, 19.0), 4.8 (1H, t, J=9.6, 18.7), 4.2 (1H, dd, J=3.7, 18.9), 2.2 (2H, m), 1.0 (3H, t, J=7.4, 14.9). ESI-MS: 246.4 (M+H)., 99395-88-7

Other significant industrial processes that involve the use of heterogeneous catalysts include the preparation of sulfuric acid, the preparation of ammonia, the oxidation of ammonia to nitric acid, and the synthesis of methanol. 99395-88-7, if you are interested, you can browse my other articles.

Reference£º
Patent; Zhang, Qiang; Zhang, Rongxia; Tian, Guanghui; Li, Jianfeng; Zhu, Fuqiang; Jiang, Xiangrui; Shen, Jingshan; US2014/46074; (2014); A1;,
Oxazolidine – Wikipedia
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2346-26-1, The molecularity of an elementary reaction is the number of molecules that collide during that step in the mechanism. If there is only a single reactant molecule in an elementary reaction, that step is designated as unimolecular. 2346-26-1, name is Oxazolidine-2,4-dione. A new synthetic method of this compound is introduced below.

A solution of 1.4 g (7.36 mmol) of 2-[4-(trifluoromethyl)phenyl]ethanol, 2.22 g (8.47 mmol) of triphenylphosphine and 0.82 g (8.1 mmol) of 1,3-oxazolidine-2,4-dione (J. Med. Chem. 1991, 34, 1542-1543) in 25 ml of tetrahydrofuran, cooled to approximately -10 C., is admixed dropwise under an inert atmosphere with a solution of 1.7 g (8.47 mmol) of diisopropyl azidocarboxylate (DIAD) in 5 ml of tetrahydrofuran, while maintaining the temperature of the reaction mixture between -10 C. and 0 C. Stirring is continued at 0 C. for 1 hour and then at 25 C. for 20 hours. The filtrate is concentrated under reduced pressure and the residue is taken up in dichloromethane and aqueous 5% sodium hydroxide solution (10 ml). The aqueous phase is separated and then extracted twice with dichloromethane. The organic phases are combined and washed in succession with aqueous hydrochloric acid solution (1N) and then saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution. The organic phase is dried over sodium sulphate and the filtrate is concentrated under reduced pressure. The residue thus obtained is purified by chromatography on silica gel, eluting with a 20/80 mixture of ethyl acetate and cyclohexane. This gives 1.5 g of oxazolidinedione in the form of an oil, 2346-26-1

Any one of these steps may be slow and thus may serve as the rate determining step. In general, however, in the presence of the catalyst, the overall rate of the reaction is faster than it would be if the reactants were in the gas or liquid phase.

Reference£º
Patent; Sanofi-Aventis; US2006/14830; (2006); A1;,
Oxazolidine – Wikipedia
Oxazolidine | C3H7NO – PubChem

95715-86-9, The molecularity of an elementary reaction is the number of molecules that collide during that step in the mechanism. If there is only a single reactant molecule in an elementary reaction, that step is designated as unimolecular. 95715-86-9, name is Methyl (R)-N-Boc-2,2-dimethyloxazolidine-4-carboxylate. A new synthetic method of this compound is introduced below.

4-Hvdroxymethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (35b). A 250-ml two-necked flask was equipped with a magnetic stirring bar, reflux condenser bearing a drying tube and a dropping funnel. The flask was charged with tetrahydrofuran (100 ml) and lithium aluminium hydride (2.16 g, 57.0 mmol). While the suspension in the flask was stirred, a solution of the ester 12a (9.90 g, 38.2 mmol) in THF (50 ml) was added dropwise during 20 min. The reaction was monitored by thin layer chromatography. When the reaction was finished, the mixture was cooled in an ice bath and a solution of 10% potassium hydroxide (20 ml) was added dropwise during 10 min. The mixture was stirred for 2 h at room temperature, whereafter the white precipitate was removed by filtration through celite. The combined organic filtrates were washed with 100 ml of aqueous phosphate buffer (pH 7), and the aqueous layer was extracted with ether. The combined organic phases were dried and concentrated which gave the title compound (8.3 g, 94%). The residue was used without further purification.

There are, however, a few established termolecular elementary reactions. The reaction of nitric oxide with oxygen appears to involve termolecular steps. you can also browse my other articles about95715-86-9

Reference£º
Patent; MEDIVIR AB; WO2009/53277; (2009); A1;,
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875444-08-9, One of the major reasons is to use measurements of the macroscopic properties of a system, the rate of change in the concentration of reactants or products with time, to discover the sequence of events that occur at the molecular level. 875444-08-9, introduce a new downstream synthesis route.

875444-08-9, Synthesis of (4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-3-((4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl)d2-methyl)-4-methyl-1,3-oxazolidin-2-one (Compound 176). A solution of 18a (495 mg) in DMF (6 mL) was cooled to -20 C. and a 1M solution of NaHMDS in THF (1.7 mL) was added slowly at <-15 C. Five minutes after the addition was complete, a solution of 17b (480 mg) in DMF (3.5 mL) was added dropwise, keeping the temperature at <-15 C. The reaction was allowed to warm slowly to 16 C. over 2 hr, and stirred for an additional 2 hr. The reaction mixture was diluted with MTBE (200 mL), washed with water (10 mL*2), dilute HCl, then brine, dried (Na2SO4), filtered and the solvent concentrated under reduced pressure to give crude Compound 176. MS m/z=640 (M=H), 662 (M+Na). There are, however, a few established termolecular elementary reactions. The reaction of nitric oxide with oxygen appears to involve termolecular steps. you can also browse my other articles about875444-08-9 Reference£º
Patent; CONCERT PHARMCEUTICALS, INC.; US2008/242711; (2008); A1;,
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80-65-9, The molecularity of an elementary reaction is the number of molecules that collide during that step in the mechanism. If there is only a single reactant molecule in an elementary reaction, that step is designated as unimolecular. 80-65-9, name is 3-Aminooxazolidin-2-one. A new synthetic method of this compound is introduced below.

General procedure: Following the addition of 4-(4-fluorophenoxy) butyric acid (0.71 g, 3.6 mmol) to 20 mL ofdichloromethane in a 50 mL three-necked round-bottom flask, thesolution was agitated until dissolution. Subsequently, EDCI (0.85 g,4.44 mmol) HOBt (0.6 g, 4.44 mmol) and triethylamine (0.84 g,9.25 mmol) were added in turn at 0 C. Stirring in an ice bath for 1 h,3-amino-2-oxazolidinone (0.37 g, 3.6 mmol) was added again. Thesolutionwas brought to 25 C and stirred overnight. Following TLC,the product was filtered by vacuum and dried under rotary evaporation.The product was a white solid weighing 0.51 g with a yieldof 50.2%.

In every case, we must determine the overall rate law from experimental data and deduce the mechanism from the rate law (and sometimes from other data). you can also browse my other articles about 80-65-9 if you are interested.

Reference£º
Article; Jiang, Kai; Yan, Xinlin; Yu, Jiahao; Xiao, Zijian; Wu, Hao; Zhao, Meihua; Yue, Yuandong; Zhou, Xiaoping; Xiao, Junhai; Lin, Feng; European Journal of Medicinal Chemistry; vol. 194; (2020);,
Oxazolidine – Wikipedia
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The molecularity of an elementary reaction is the number of molecules that collide during that step in the mechanism., 95530-58-8, If there is only a single reactant molecule in an elementary reaction, that step is designated as unimolecular. 95530-58-8, name is (R)-4-Isopropyloxazolidin-2-one. A new synthetic method of this compound is introduced below.

A mixture of 2-(3-bromo-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (600 mg, 1.7 mmol), (R)-4-isopropyl-2-oxazolidinone (322 mg, 2.5 mmol), copper(I) iodide (96 mg, 0.5 mmol), N,N-dimethylglycine hydrochloride (140 mg, 1.0 mmol) and potassium carbonate (923 mg, 6.7 mmol) in dimethyl sulfoxide (5 mL) was stirred at 120 C. for 16 h. Then the reaction mixture cooled to room temperature. The reaction mixture was extracted with ethyl acetate (2¡Á150 mL), washed with water (2¡Á50 mL) and saturated aqueous ammonium chloride solution (2¡Á50 mL), dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by Waters automated flash system (column: Xterra 30 mm¡Á100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded 2-[3-((R)-4-isopropyl-2-oxo-oxazolidin-3-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (555 mg, 80%) as a white solid: LC/MS m/e calcd for C24H28N2O4 (M+H)+: 409.50, observed: 409.1.

Any one of these steps may be slow and thus may serve as the rate determining step. In general, however, in the presence of the catalyst, the overall rate of the reaction is faster than it would be if the reactants were in the gas or liquid phase.

Reference£º
Patent; Chen, Li; Feng, Lichun; Huang, Mengwei; Liu, Yongfu; Wu, Guolong; Wu, Jim Zhen; Zhou, Mingwei; US2011/257151; (2011); A1;,
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1121-83-1, The molecularity of an elementary reaction is the number of molecules that collide during that step in the mechanism. If there is only a single reactant molecule in an elementary reaction, that step is designated as unimolecular. 1121-83-1, name is 5,5-Dimethyloxazolidin-2-one. A new synthetic method of this compound is introduced below.

To a solution of 6-(6-fluoro-4-iodo-2-pyridyl)-5-methyl-2-pyrimidin-2-yl-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine (the product of step 1 in Example 96, 100 mg, 223 muiotaetaomicron) in dioxane (3mL) was added 5,5-dimethyloxazolidin-2-one (51.4 mg, 446 muiotaetaomicron), cesium carbonate (145 mg, 446 muiotaetaomicron), Xantphos (25.8 mg, 44.6 muiotaetaomicron) and Pd(OAc)2(5.01 mg, 22.3 muiotaetaomicron). The reaction mixture was heated at 100 C with stirring for 20 hrs under Ar. After being cooled to rt, the resulting mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by prep-HPLC to give 3-[2-Fluoro-6-(5-methyl-2-pyrimidin-2-yl-7,8-dihydro-5H-pyrido [4,3-d]pyrimidin-6-yl)-4-pyridyl]-5,5-dimethyl-oxazolidin-2-one (8 mg) as a light yellow solid. 1H NMR (400MHz, DMSO-<) delta ppm: 8.99 (d, 2H), 8.95 (s, 1H), 7.64 (t, 1H), 6.72 (s, 6.70 (s, 1H), 5.71-5.66 (m, 1H), 4.51 - 4.40 (m, 1H), 3.93 (s, 2H), 3.56 - 3.44 (m, 1H), 3.12 - 2.97 (m, 2H), 1.53 (d, 3H), 1.49 (d, 6H). MS obsd (ESI) [(M+H)+]: 436. In every case, we must determine the overall rate law from experimental data and deduce the mechanism from the rate law (and sometimes from other data). you can also browse my other articles about 1121-83-1 if you are interested. Reference£º
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; CHENG, Zhanling; HAN, Xingchun; JIANG, Min; WANG, Jianhua; WANG, Yongguang; YANG, Song; (211 pag.)WO2018/1952; (2018); A1;,
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