Category: esters-buliding-blocks

Reference of 6962-92-1, These common heterocyclic compound, 6962-92-1, name is 4-Chlorobutyl acetate, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Preparation 6 To an ice-cooled solution of 3-(3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazolo[1,5-a]pyridine (2.0 g) in N,N-dimethylformamide (20 ml) was added portionwise sodium hydride (60% dispersion in mineral oil; 0.31 g). After addition was finished, the mixture was stirred for 15 minutes in an ice-bath. To this mixture was added 4-chlorobutyl acetate (1.1 g), and the reaction mixture was stirred for 24 hours at room temperature, and then for 36 hours at 70 C. After being cooled to room temperature, the reaction mixture was concentrated. The residue was partitioned between ethyl acetate and water. The organic layer was separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with water and sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and concentrated. Purification of the residue by column chromatography on silica gel (using 3:1 mixture of chloroform and ethyl acetate as eluent) gave 3-[2-(4-acetoxybutyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine (2.6 g). An analytical sample was prepared by recrystallization from diisopropyl ether. mp: 102-103 C. IR (Nujol): 1720, 1660 cm-1 NMR (CDCl3, delta): 1.7-1.9 (2H, m), 1.9-2.2 (2H, m), 2.05 (3H, s), 4.16 (2H, t-like, J=ca. 6Hz), 4.31 (2H, t-like, J=ca. 6Hz), 6.77 (1H, d, J=10Hz), 6.8-7.0 (1H, m), 7.02 (1H, d, J=10Hz), 7.2-7.4 (1H, m), 7.4-7.5 (3H, m), 7.6-7.7 (2H, m), 7.9-8.0 (1H, m), 8.5-8.6 (1H, m) MASS m/z: 402, 343, 287 Anal. Calcd. for C23 H22 N4 O3: C 68.64, H 5.51, N 13.92 (%) Found: C 68.31, H 5.48, N 13.76 (%)

The synthetic route of 6962-92-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Fujisawa Pharmaceutical Co., Ltd.; US5338743; (1994); A;,
Ester – Wikipedia,
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These common heterocyclic compound, 66315-16-0, name is Methyl 3-amino-4-(methylamino)benzoate, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. category: esters-buliding-blocks

DCC (12.3 g, 59.7 MMOL) was added to an ice-water cooled solution of N-BOC 8-alanine (10.0 g, 52.8 MMOL) and methyl 3-amino-4-methylaminobenzoate (8.27 g, 45.9 MMOL) in CH2CI2 (400 mL). The reaction mixture was stirred 1 h at 0C and overnight at room temperature, then the insoluble urea was removed by filtration. After concentration, the residue was dissolved in ethyl acetate and washed with 5% NAHCO3, followed with saturated NaCl. The organic solution was dried over NA2SO4, concentrated, and purified by chromatography over silica gel eluted with 1: 2 hexane-EtOAc to afford 15.02 g (93%) of desired product as a white SOLID. 1H NMR (300 MHz, D6-DMSO) o 9.06 (s, 1H), 7.70 (d, J=1.8 Hz, 1 H), 7.66 (dd, J=8.4 Hz, J=1.8 Hz, 1 H), 6.87 (s, 1 H), 6.59 (d, J=8.4 Hz, 1 H), 5.89 (d, J=4.8 Hz, 1 H), 3.74 (s, 3H), 3.23 (q, J=6.9 Hz, 2H), 2.76 (d, J=4.8 Hz, 3H), 2.46 (t, J=6.9 Hz, 2H), 1.38 (s, 9H). Anal. Calc’d. FORC17H25N305 : C, 58.11 ; H, 7.17 ; N, 11.96. Found: C, 58.28 ; H, 7.09 ; N, 11.92.

The synthetic route of Methyl 3-amino-4-(methylamino)benzoate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PHARMACIA CORPORATION; WO2004/99131; (2004); A2;,
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Ester – an overview | ScienceDirect Topics

Reference of 927-68-4, A common heterocyclic compound, 927-68-4, name is 2-Bromoethyl acetate, molecular formula is C4H7BrO2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

To a 250 mL flask equipped with magnetic stirring bar, 1-(3-fluoro-2-nitrophenyl)piperazine A-6 (5 g, 22.5 mmol) was added under argon atmosphere and the flask was filled with dry ACN (50 mL). Then, dried K2CO3 (6,0 g, 45 mmol) and 2-bromoethyl acetate (4.45 g, 26.6 mmol) were added, and the reaction mixture was heated to 60 C and stirred for 20h at this temperature. After this time UPLCMS analysis showed no substrate peak. The reaction was cooled to room temperature and solid was filtered. As a result, the product A-2C was obtained as the yellow solid (6.8 g, 99% yield) with 99 % of purity, according to UPLCMS analysis (Method A).

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; Adamed sp. z o.o.; KOLACZKOWSKI, Marcin; BUCKI, Adam; SNIECIKOWSKA, Joanna; MARCINKOWSKA, Monika; (65 pag.)EP3530651; (2019); A1;,
Ester – Wikipedia,
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In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 185312-82-7, name is Methyl 4-bromo-2-chlorobenzoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. HPLC of Formula: C8H6BrClO2

To a stirred solution of 4-bromo-2-chlorobenzoic acid, methyl ester (18.69 g) in triethylamine (110 ml), was added 1-dimethylamino-2-propyne (12.1 ml), bis(triphenylphosphine)palladium(II) chloride (1.26 g), and copper(I) iodide (0.136 g). The mixture was heated slowly to 60 C., and the temperature maintained for one hour. The reaction was cooled to room temperature, filtered through diatomaceous earth, and the collected solid washed with ethyl acetate. The solvent was removed in vacuo, the resulting residue redissolved in ethyl acetate, and washed with water (3¡Á). The combined organic extract was dried over anhydrous sodium sulfate, and the solvent removed in vacuo to give a crude product. The crude product was purified by column chromatography on silica gel (225 g), eluting with 40% ethyl acetate/hexane. After removing the solvent in vacuo, the title compound was obtained as a viscous oil (17.7 g), MS (+FAB), m/z: 252 (M+H)+.

The synthetic route of 185312-82-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; American Cyanamid Company; US6831079; (2004); B1;,
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Synthetic Route of 91367-05-4,Some common heterocyclic compound, 91367-05-4, name is Methyl 4-chloro-3-methylbenzoate, molecular formula is C9H9ClO2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

To a solution of methyl 4-chloro-3-methylbenzoate (5.0 g, 27.0 mmol) in THF (30 ml.) at 00C, LHMDS (1.0 M in THF, 57 ml_, 57 mmol) was added and the solution was allowed to stir for 5 min. A solution of 2-chloro-4-methylpyrimidine (3.47 g, 27.0 mmol) dissolved in THF (8 ml.) was added dropwise at 00C and the reaction mixture was allowed to stir for 30 min. The reaction mixture was quenched at 00C with MeOH (50 ml.) and the solvent was removed in vacuo. The residue was diluted with EtOAc and washed with water. The organic layer was dried over MgSO4, filtered and evaporated. The title compound of Step A was purified by trituration with EtOAc. The title compound of Step A was obtained as a solid in 20% yield (1.5 g). MS (APCI): 281.1 [M+H]+.

The synthetic route of 91367-05-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2009/32667; (2009); A1;,
Ester – Wikipedia,
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Reference of 125568-73-2,Some common heterocyclic compound, 125568-73-2, name is Methyl 5-amino-2,4-difluorobenzoate, molecular formula is C8H7F2NO2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

A solution of methyl 5-amiotano-2,4-diotafluorobenzoate intermediate 19 (5 5 g, 29 5 mmol, 1 equiv) in dichloromethane (100 mL) at -40 0C was treated with pyridine (7 16 mL, 88 6 mmol, 3 0 equiv) and 1 9 M phosgene in toluene (23 3 mL, 44 3 mmol, 1 5 equiv) After 1 5 h, a solution of 1 ,1-diotamethylethyl 4-(butylamiotano)-1-piotaperiotadiotanecarboxylate intermediate 20 (9 1 g, 35 4 mmol, 1 2 equiv) in dichloromethane (50 mL) was added and the reaction was allowed to warm to RT for 18 h The reaction was diluted with dichloromethane, washed with satd aq NaHCO3, dried over Na2SO4, filtered and concentrated to give intermediate 21 (13 1 g, 95% yield) a white solid1H NMR (400 MHz, DMSO-cfe) delta ppm 8 09 (s, 1 H), 7 89 – 7 99 (m, 1 H), 7 42 (t, J=10 62 Hz, 1 H), 3 88 – 3 99 (m, 1 H), 3 85 (s, 3 H), 3 11 – 3 22 (m, 2 H), 2 96 (d, J=12 27 Hz, 2 H), 2 41 – 2 53 (m, 3 H), 1 43 – 1 59 (m, 5 H), 1 21 – 1 35 (m, 2 H), 1 20 (s, 9 H), 0 90 (t, J=I 33 Hz, 3 H) ES-LCMS m/z 468 1 (M-H); Intermediate 291 ,1-diotamethylethyl 4-[[({2,4-diotafluoro-5-[(methyloxy)carbonyl]phenyl}amiotano)carbonyl](3- fluorophenyl)amiotano]-1-piotaperiotadiotanecarboxylateA solution of methyl 5-amiotano-2,4-diotafluorobenzoate intermediate 19 (5 O g, 26 5 mmol, 1 equiv) in dichloromethane (150 mL) at -40 0C was treated with pyridine (6 4 mL, 79 7 mmol, 3 0 equiv) and 1 9 M phosgene in toluene (20 1 mL, 39 8 mmol, 1 5 equiv) After 1 5 h, the reaction was concentrated down and dried under vac The residue was taken up in dichloromethane (150 mL) and 1 ,1-diotamethylethyl 4-[(3-fluorophenyl)amiotano]-1- piperidmecarboxylate intermediate 6 (8 6 g, 29 2 mmol, 1 1 equiv) was added and the reaction was heated to 40 0C 18 h The reaction was diluted with dichloromethane, washed with satd aq NaHCO3, dried over Na2SO4, filtered and concentrated The residue was purified by silica gel flash column chromatography (0 ? 30% ethyl acetate hexanes) to give intermediate 29 (12 6 g, 94% yield) a white solid1H NMR (400 MHz, CHLOROFORM-d) delta ppm 8 65 (dd, J=8 88, 7 78 Hz, 1 H), 744 – 7 55 (m, 1 H), 7 17 – 7 24 (m, 1 H), 7 04 (d, J=I 87 Hz, 1 H), 6 92 – 6 99 (m, 1 H), 6 80 (t, J=10 26 Hz, 1 H), 5 96 (d, J=Z 11 Hz, 1 H), 4 56 – 4 70 (m, 1 H), 4 03 – 4 26 (m, 2 H), 3 80 – 3 92 (m, 3 H), 2 79 (s, 2 H), 1 85 (d, J=13 37 Hz, 2 H), 1 39 (s, 9 H), 1 19 – 1 35 (m, 2 H) ES-LCMS m/z 530 1 (M+Na)

The synthetic route of 125568-73-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2009/75960; (2009); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 17100-65-1, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 17100-65-1 as follows.

[0162] Step c: To a reaction vial containing 7-amino-4-chloro-isoindolin-l-one (250 mg, 1.37 mmol) in dioxane (10 mL) was added methyl 2-bromo-5-methoxy-benzoate (502 mg, 2.05 mmol), cesium carbonate (893 mg, 2.74 mmol), copper iodide (104 mg, 0.55 mmol) and (1S,2S)- Nl,N2-dimethylcyclohexane-l,2-diamine (156 mg, 1.1 mmol). The mixture was purged with nitrogen, then warmed to 110 C. The reaction was stirred at 110 C for lh and the reaction was monitored by LC-MS. Following completion, the reaction was allowed to cool and was then filtered through Celite and rinsed with ethyl acetate. The crude was purified by silica gel chromatography (0-50% ethyl acetate/hexane) to give methyl 2-(7-amino-4-chloro-l-oxo- isoindolin-2-yl)-5-methoxy-benzoate. MS: (ES) m/z calculated for CI7HI5C1N204[M+H]+347.1, found 347.1.

According to the analysis of related databases, 17100-65-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CHEMOCENTRYX, INC.; CHEN, Xi; DRAGOLI, Dean, R.; FAN, Junfa; KALISIAK, Jaroslaw; LELETI, Manmohan, Reddy; MALATHONG, Viengkham; MCMAHON, Jeffrey; TANKAKA, Hiroko; YANG, Ju; YU, Chao; ZHANG, Penglie; MALI, Venkat; (104 pag.)WO2017/87610; (2017); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Application of 105-76-0, These common heterocyclic compound, 105-76-0, name is Dibutyl maleate, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

EXAMPLE 6 Dibutyl N-Hydroxyaspartate Hydroxylamine free base (50% aqueous solution, 8.0 g, 0.12 mol) was added dropwise to dibutyl maleate (25.0 g, 0.1 mol) in a 3-neck 250 ml flask blanketed with nitrogen. The reaction temperature was maintained below 55 C. with an ice bath. The mixture was stirred for 30 minutes. The gas liquid chromatography (GLC) analysis of the reaction mixture indicated 96% conversion of dibutyl maleate. The NMR analysis showed that the reaction mixture contained dibutyl N-hydroxyaspartate in greater than 95% purity.

The synthetic route of 105-76-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Hoechst Celanese Corporation; US5322948; (1994); A;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 17205-02-6, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 17205-02-6 name is Ethyl 3-hydroxycyclobutanecarboxylate, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

[0729] To a solution of ethyl 3-hydroxycyclobutanecarboxylate (10.2 g, 78.4 mmol) in dry pyridine (56.5 mL) at ooC., TsCI (14.9 g, 78.4 mmol) was added portionwise. Theresulting mixture was stirred at rt overnight. The reactionmixture was concentrated under reduced pressure and theresidue obtained was dissolved in EtOAc (100 mL) andsequentially washed with 2 N HCI (100 mL), saturatedNaHC03 (100mL)andwater(100mL). TheEtOAclayerwasdried over Na2S04 , filtered, and concentrated to obtain ethyl3-(tosyloxy)cyclobutanecarboxylate as a pale yellow oil,which was used in the next step without further purification.[0730] To a solution ethyl 3-(tosyloxy)cyclobutanecarboxylate (6.0 g, 20 mmol, as prepared above) in anhydrousMEK(20mL), Nal (7.5 g, 50mmol)was added. Theresultingmixture was heated at 120 C. for 4 h in a microwave reactor.The reaction mixture was concentrated and water (50 mL)was added. The resultant mixture was extracted with ether(100mL) and washed with 10% Na2 S 20 3 (50mL) and water(50 mL). The ether layer was separated, dried over Na2S04 ,filtered, and concentrated. The residue was distilled underreduced pressure to obtainthe title compound 43a as a cis andtrans mixture. 1 H-NMR (400 MHz, CDCI 3 ) o (ppm): 4.66(quin, 1=7.2 Hz, lH), 4.30-4.48 (m, 2H), 4.02-4.24 (m, 6H),3.30-3.49 (m, lH), 3.03-3.21 (m, 2H), 2.64-3.02 (m, 12H),1.18-1.34 (m, 9H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl 3-hydroxycyclobutanecarboxylate, and friends who are interested can also refer to it.

Reference:
Patent; JANSSEN PHARMACEUTICA, NV; Player, Mark R.; Meegalla, Sanath K.; Illig, Carl R.; Chen, Jinsheng; Wilson, Kenneth J.; Lee, Yu-Kai; Parks, Daniel J.; Huang, Hui; Patel, Sharmila; Lu, Tianbao; US2014/364414; (2014); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 18595-18-1 as follows. SDS of cas: 18595-18-1

To a solution of 6,7-bis-(2-methoxy-ethoxy)-2-oxo-1,2-dihydro-quinoline-3-carboxylic acid (0.1 g, 0.30 mmol) in DMF (5 mL) was added HATU (0.137 g, 0.36 mmol) (Aldrich), triethylamine (0.1 mL, 0.72 mmol) (Fluka) and 3-amino-4-methyl-benzoic acid methyl ester (0.059 g, 0.36 mmol) (TCI). The reaction mixture was stirred at room temperature for 18 hours. Then, water (5 mL), saturated aqueous sodium bicarbonate solution (5 mL) and ethyl acetate (10 mL) were added. After mixing, the precipitate was filtered under vacuum and washed with ethyl acetate. The resulting solid was dried under air to provide 3-{[6,7-bis-(2-methoxy-ethoxy)-2-oxo-1,2-dihydro-quinoline-3-carbonyl]-amino}-4-methyl-benzoic acid methyl ester(1-phenyl-propyl)-amide. (Yield 0.064 g, 55%). HR-MS (ES+) m/z Calculated for C25H29N2O8 ([M+H]+): 485.1919. Found: 485.1919.

According to the analysis of related databases, 18595-18-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Dominique, Romyr; Luk, Kin-Chun; Qiao, Qi; Rossman, Pamela Loreen; US2012/184548; (2012); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics