[ CAS No. 3878-55-5 ] {[proInfo.proName]}

Name: 3878-55-5|4-Methoxy-4-oxobutanoic acid|97%
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SKU: A112240
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Quality Control of [ 3878-55-5 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 3878-55-5 ]

Product Details of [ 3878-55-5 ]

CAS No. :	3878-55-5	MDL No. :	MFCD00002788
Formula :	C₅H₈O₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JDRMYOQETPMYQX-UHFFFAOYSA-N
M.W :	132.11	Pubchem ID :	77487
Synonyms :

Calculated chemistry of [ 3878-55-5 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.6
Num. rotatable bonds :	4
Num. H-bond acceptors :	4.0
Num. H-bond donors :	1.0
Molar Refractivity :	29.21
TPSA :	63.6 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.09 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.08
Log Po/w (XLOGP3) :	0.02
Log Po/w (WLOGP) :	0.02
Log Po/w (MLOGP) :	-0.13
Log Po/w (SILICOS-IT) :	-0.14
Consensus Log Po/w :	0.17

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-0.41
Solubility :	51.7 mg/ml ; 0.391 mol/l
Class :	Very soluble
Log S (Ali) :	-0.91
Solubility :	16.3 mg/ml ; 0.124 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.1
Solubility :	104.0 mg/ml ; 0.785 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.56

Safety of [ 3878-55-5 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 3878-55-5 ]

* 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.

Upstream synthesis route of [ 3878-55-5 ]
Downstream synthetic route of [ 3878-55-5 ]

[ 3878-55-5 ] Synthesis Path-Upstream 1~6

1
[ 3878-55-5 ]
[ 3395-91-3 ]

Reference： [1] Journal of Organic Chemistry, 1969, vol. 34, # 4, p. 1172 - 1173

2
[ 3878-55-5 ]
[ 37517-81-0 ]

Reference： [1] Patent: CN105503746, 2016, A, . Location in patent: Paragraph 0054; 0055; 0056

3
[ 6654-36-0 ]
[ 3878-55-5 ]
[ 1501-27-5 ]
[ 627-91-8 ]

Reference： [1] Journal de Chimie Physique et de Physico-Chimie Biologique, 1995, vol. 92, # 7-8, p. 1344 - 1364

4
[ 3878-55-5 ]
[ 75-65-0 ]
[ 42116-55-2 ]

Reference： [1] Chemical and Pharmaceutical Bulletin, 1974, vol. 22, # 8, p. 1795 - 1799

5
[ 3878-55-5 ]
[ 100-51-6 ]
[ 54755-77-0 ]

Reference： [1] Journal of Organic Chemistry, 1982, vol. 47, # 24, p. 4605 - 4611

6
[ 3878-55-5 ]
[ 2216-51-5 ]
[ 77341-67-4 ]

Reference： [1] Journal of the Chemical Society, 1922, vol. 121, p. 2055

[ 3878-55-5 ] Synthesis Path-Downstream 1~51

1
[ 110-86-1 ]
[ 67-56-1 ]
[ 3878-55-5 ]
[ 54322-10-0 ]
[ 124-41-4 ]
[ 505-48-6 ]
[ 627-93-0 ]
[ 20291-40-1 ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1954,vol. 19,p. 716

2
[ 32231-50-8 ]
[ 3878-55-5 ]
[ 2177-82-4 ]

Reference： [1]Huaxue Xuebao/Acta Chimica Sinica,1959,vol. 25,p. 129,134
Chem.Abstr.,1960,p. 4365

3
[ 53663-30-2 ]
[ 3878-55-5 ]
[ 2768-16-3 ]

Reference： [1]Journal of the Chemical Society,1959,p. 3258,3263

4
[ 3878-55-5 ]
[ 373-49-9 ]
[ 506-17-2 ]

Reference： [1]Journal of the Chemical Society,1954,p. 4219,4223

5
[ 3878-55-5 ]
[ 54947-74-9 ]
[ 53696-14-3 ]

Reference： [1]Journal of the Chemical Society,1953,p. 1538,1540

6
[ 3878-55-5 ]
[ 2216-51-5 ]
[ 77341-67-4 ]

Reference： [1]Journal of the Chemical Society,1922,vol. 121,p. 2055

7
[ 3878-55-5 ]
[ 1634-09-9 ]
[ 102162-64-1 ]

Reference： [1]Cagniant; Cagniant [Bulletin de la Societe Chimique de France, 1958, p. 1448,1457]

8
[ 3878-55-5 ]
[ 634-36-6 ]
[ 51686-50-1 ]

Yield	Reaction Conditions	Operation in experiment
72%	With PPA; Polyphosphoric acid (PPA) at 45℃; for 2.5h;	2 4-Oxo-4-(2,3,4-trimethoxy-phenyl)-butyric acid methyl ester (55) 4-Oxo-4-(2,3,4-trimethoxy-phenyl)-butyric acid methyl ester (55) A mixture of 75 g of polyphosphoric acid (Acros), 1,2,3-trimethoxybenzene (5.0 g, 29.73 mmol), and mono-methyl succinate (5.9 g, 44.59 mmol) were mechanically stirred at 45° C. for 2.5 h. The reaction mixture was then poured into a 1000 mL beaker containing round 250 mL of ice, and stirred well until all the product was precipitated out. The tan colored product was then filtered and washed with water and dried under vacuum. 6.1 g (72%) of 55 was obtained, which was pure by NMR. 1H NMR (CDCl3, 300 MHz): δ 7.56 (d, J=8.89 Hz, 1H), δ 6.72 (d, J=8.91 Hz, 1 H), δ 3.99 (s, 3H), δ 3.91 (s, 3H), δ 3.87 (s, 3H), δ 3.70 (s, 3H), δ 3.31 (t, J=6.57, 2H), δ 2.71 (t, J=6.57 Hz, 2H).
70%	With PPA
	With PPA

Reference： [1]Current Patent Assignee: BAYLOR UNIVERSITY - US2006/293394, 2006, A1 Location in patent: Page/Page column 29
[2]Khanolkar, Atmaram D.; Lu, Dai; Fan, Pusheng; Tian, Xiaoyu; Makriyannis, Alexandros [Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 15, p. 2119 - 2124]
[3]Gardner [Journal of the American Chemical Society, 1954, vol. 76, p. 4550]

9
[ 19975-56-5 ]
[ 3878-55-5 ]
[ 60437-68-5 ]

Reference： [1]Chemistry Letters,1976,p. 711 - 714

10
[ 3878-55-5 ]
[ 24316-19-6 ]
[ 61568-57-8 ]

Reference： [1]Journal of Medicinal Chemistry,1977,vol. 20,p. 328 - 332

11
[ 3878-55-5 ]
[ 75-65-0 ]
[ 42116-55-2 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1974,vol. 22,p. 1795 - 1799

13
[ 14734-25-9 ]
[ 3878-55-5 ]

Reference： [1]Synlett,2002,p. 826 - 828
[2]Synthetic Communications,1983,vol. 13,p. 523 - 530

14
[ 3878-55-5 ]
[ 115-11-7 ]
[ 14734-25-9 ]

Reference： [1]Tetrahedron,1987,vol. 43,p. 4635 - 4648
[2]Tetrahedron Letters,1988,vol. 29,p. 757 - 760

15
[ 3878-55-5 ]
[ 41827-15-0 ]
[ 41826-92-0 ]

Yield	Reaction Conditions	Operation in experiment
	(i) polyphosphoric acid, (ii) aq. AcOH; Multistep reaction;

Reference： [1]Murata; Satoh; Nohara; et al. [European Journal of Medicinal Chemistry, 1977, vol. 12, # 1, p. 17 - 20]

16
[ 3878-55-5 ]
[ 173990-76-6 ]
[ 748110-12-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tetrahydroborate 1.) toluene, 0 deg C - 10 deg C, 2.) toluene, reflux, 4 h; Multistep reaction;

Reference： [1]Namil, A.; Benoit-Guyod, M.; Leclerc, G. [European Journal of Medicinal Chemistry, 1995, vol. 30, # 12, p. 973 - 982]

17
[ 3878-55-5 ]
[ 13375-29-6 ]
[ 176797-41-4 ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 2379 - 2391

18
[ 3878-55-5 ]
[ 38330-80-2 ]
[ 5457-44-3 ]

Yield	Reaction Conditions	Operation in experiment
70%		The alpha-hydromuconic acid used in the present invention was prepared by chemical synthesis. First, 1.5 L of super-dehydrated tetrahydrofuran (manufactured by Wako Pure Chemical Industries, Ltd.) was added to 13.2 g (0.1 mol) of succinic acid monomethyl ester (manufactured by Wako Pure Chemical Industries, Ltd.), and 16.2 g (0.1 mol) of carbonyldiimidazole (manufactured by Wako Pure Chemical Industries, Ltd.) was added thereto with stirring, followed by stirring the resulting mixture under nitrogen atmosphere for 1 hour at room temperature. To this suspension, 15.6 g (0.1 mol) of <strong>[38330-80-2]malonic acid monomethyl ester potassium salt</strong> and 9.5 g (0.1 mol) of magnesium chloride were added. The resulting mixture was stirred under nitrogen atmosphere for 1 hour at room temperature, and then stirred at 40 C. for 12 hours. After the reaction, 0.05 L of 1 mol/L hydrochloric acid was added to the mixture, and extraction with ethyl acetate was carried out. By separation purification by silica gel column chromatography (hexane:ethyl acetate=1:5), 13.1 g of pure 3-oxohexanedicarboxylic acid dimethyl ester was obtained. Yield: 70%.
70%		First, 1.5 L of super-dehydrated tetrahydrofuran (manufactured by Wako Pure Chemical Industries, Ltd.) was added to 13.2 g (0.1 mol) of succinic acid monomethyl ester (manufactured by Wako Pure Chemical Industries, Ltd.), and 16.2 g (0.1 mol) of carbonyldiimidazole (manufactured by Wako Pure Chemical Industries, Ltd.) was added thereto with stirring, followed by stirring the resulting mixture under nitrogen atmosphere at room temperature for 1 hour. To this suspension, 15.6 g (0.1 mol) of <strong>[38330-80-2]malonic acid monomethyl ester potassium salt</strong> and 9.5 g (0.1 mol) of magnesium chloride were added. The resulting mixture was stirred under nitrogen atmosphere at room temperature for 1 hour, and then stirred at 40 C. for 12 hours. Afier completion of the reaction, 0.05 L of 1 mol/L hydrochloric acid was added to the mixture at room temperature, and extraction with ethyl acetate was carried out. By separation and purification by silica gel column chromatography (hexane:ethyl acetate=1:5), 13.1 g of pure 3-oxohexanedicarboxylic acid dimethyl ester was obtained. Yield: 70%.
		Add 30g of monomethyl succinate and 260mL of tetrahydrofuran to a 500mL three-neck round bottom flask and add in batches.40.5 g of carbonyl diimidazole, stirred at room temperature for 1 hour,Then, 35.46 g of <strong>[38330-80-2]monomethyl malonate potassium salt</strong> and 21.62 g of magnesium chloride were added, and the reaction was stirred at 40 C for 15 hours. After the TLC detection reaction was completed, the solvent was distilled off.Adding 180 mL of acetic acid for acidification,The salt is removed by filtration to give an acetic acid solution of the compound of formula III.

Reference： [1]Patent: US2017/320819,2017,A1 .Location in patent: Paragraph 0048; 0049; 0052; 0053; 0056; 0057
[2]Patent: US2018/237389,2018,A1 .Location in patent: Paragraph 0074
[3]Patent: US2020/62704,2020,A1 .Location in patent: Paragraph 0096
[4]Synthesis,1999,p. 568 - 570
[5]Patent: CN109879775,2019,A .Location in patent: Paragraph 0021-0023; 0025-0027

19
[ 3878-55-5 ]
[ 10482-56-1 ]
Succinic acid methyl ester 1-methyl-1-(4-methylcyclohex-3-enyl)ethyl ester [ No CAS ]

Reference： [1]Synthesis,2001,p. 1027 - 1034

20
[ 3878-55-5 ]
[ 98-80-6 ]
[ 25333-24-8 ]

Yield	Reaction Conditions	Operation in experiment
70%	With P(p-CH₃OC₆H₄)3; 2,2-dimethylpropanoic anhydride In tetrahydrofuran; water at 60℃; for 16h;
51%	Stage #1: methyl hydrogen succinate With di(succinimido) carbonate; sodium carbonate; tricyclohexylphosphine In tetrahydrofuran at 60℃; Stage #2: phenylboronic acid In tetrahydrofuran at 60℃; for 20h; Further stages.;

Reference： [1]Goossen, Lukas J.; Ghosh, Keya [European Journal of Organic Chemistry, 2002, # 19, p. 3254 - 3267]
[2]Goossen; Ghosh [Chemical Communications, 2001, # 20, p. 2084 - 2085]

21
[ 3878-55-5 ]
[ 53587-11-4 ]
[ 221077-35-6 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 598 - 622

22
[ 3878-55-5 ]
[ 58-27-5 ]
[ 947703-36-8 ]

Yield	Reaction Conditions	Operation in experiment
58%	With ammonium persulfate; silver nitrate In water; acetonitrile at 65℃;
58%	Stage #1: methyl hydrogen succinate; menadione With silver nitrate In water; acetonitrile at 65℃; Stage #2: With ammonium peroxydisulfate In water; acetonitrile at 65℃;	42 Example 42 Synthesis of 2-methyl-1-4-naphthoquinone methyl 3-propanoate In a 100 ml flask containing 1.000 g of menadione (Aldrich Co) (1 eq.; 5.81 mmol), 2.300 of methyl monoester of succinic acid (Aldrich Co) (3 eq.; 17.40 mmol) and 0.300 g of AgNO3 (0.3 eq.; 1.80 mmol) are introduced. The CH3CN:water (2:1) mixture is added, that is to say 30.0 ml of CH3CN and 15.0 ml of H2O, and the temperature of the mixture is raised to 65° C. The addition of 1.730 g of (NH4)2S2O8 (1.3 eq.; 7.60 mmol) dissolved in 30.0 ml of a CH3CN:H2O mixture takes place over 2 hours. The reaction medium is then kept stirred for one hour at 65° C., and then extraction is carried out with CH2Cl2 three times and the organic phases are washed just once with H2O. The organic phases are dried on MgSO4 and then evaporated. The product is purified on a chromatography column with CH3OH; CH2Cl2 eluant (gradient from 0:100 to 5:95) and 0.875 g of an orange oil is recovered (yield=58%).

Reference： [1]Commandeur, Claude; Chalumeau, Celine; Dessolin, Jean; Laguerre, Michel [European Journal of Organic Chemistry, 2007, # 18, p. 3045 - 3052]
[2]Current Patent Assignee: FLUOFARMA; UNIVERSITY OF BORDEAUX 1; CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - US2009/247472, 2009, A1 Location in patent: Page/Page column 24

23
[ 3878-55-5 ]
[ 53587-11-4 ]
C₂₄H₂₅NO₁₀ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine; In dichloromethane; at 0 - 20℃;	To a mixture of <strong>[53587-11-4]L-tyrosine benzyl ester p-toluenesulfonate</strong> salt (5.0 g) and triethylamine in CH2Cl2 (25 mL) at 0 C. is added EDC (2.2 g) and monomethyl succinate (1.5 g). The mixture is warmed to room temperature and stirred overnight. The mixture is diluted with EtOAc (150 mL), and washed with 1 M HCl (50 mL), sat. NaHCO3 (50 mL), and sat. NaCI (50 mL). The organic phase is dried (MgSO4), and the solvent is removed under reduced pressure. The residue is purified by flash chromatography (SiO2, 60% EtOAc/hexane) to provide 3.4 g of title compound as a colorless oil which slowly solidified to a white solid: 1H NMR (CDCl3) delta7.33, 6.84, 6.65, 6.15, 5.62, 5.14, 4.87, 3.67, 3.01, 2.64, 2.47; MS (EI) m/z 385 (M+), 254, 209, 208, 147, 136, 132, 115, 107, 91, 55; Anal. Found: C, 65.41; H, 6.00; N, 3.61.

Reference： [1]Patent: US6353023,2002,B1 .Location in patent: Page column 30

24
[ 3878-55-5 ]
[ 73647-50-4 ]
[ 1196463-29-2 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: methyl hydrogen succinate With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran; N,N-dimethyl-formamide at 25 - 30℃; Stage #2: N'-hydroxy-3-methoxybenzenecarboximidamide With dmap In tetrahydrofuran; N,N-dimethyl-formamide

Reference： [1]Location in patent: experimental part Jadhav, Ganesh R.; Shaikh, Mohammad U.; Kale, Rajesh P.; Ghawalkar, Anand R.; Gill, Charansingh H. [Journal of Heterocyclic Chemistry, 2009, vol. 46, # 5, p. 980 - 987]

25
[ 3878-55-5 ]
[ 1594-58-7 ]
[ 1196463-25-8 ]

Reference： [1]Journal of Heterocyclic Chemistry,2009,vol. 46,p. 980 - 987

26
[ 3878-55-5 ]
[ 54872-79-6 ]
[ 1196463-28-1 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: methyl hydrogen succinate With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran; N,N-dimethyl-formamide at 25 - 30℃; Stage #2: 3-fluoro-N'-hydroxybenzenecarboximidamide With dmap In tetrahydrofuran; N,N-dimethyl-formamide

27
[ 13013-02-0 ]
[ 3878-55-5 ]

Reference： [1]Organic Letters,2010,vol. 12,p. 3618 - 3621

28
[ 175135-32-7 ]
[ 3878-55-5 ]
[ 1007788-41-1 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In chloroform for 24h;	5.1.3. General procedure for the synthesis of methyl 4-(4-(2-chlorophenyl)thiazol-2-yla-mino)-4-oxobutanoate General procedure: A mixture of 4-(2-chlorophenyl)thiazol-2-amine (500 mg, 2.37 mmol), DMAP (13.27 mg, 0.12 mmol), EDCI (682.43 mg, 3.55 mmol) and 4-methoxy-4-oxobutanoic acid (470.3 mg, 3.55 mmol) in chloroform (20 mL) was stirred at room temperature for 24 h. The solution was filtered, and filtrate was washed with water. The organic phase was dried (Na2SO4) and evaporated to dryness. The residue was purified by flash chromatography over silica gel eluting with CH2Cl2:EtOAC (80:1) yielded 280 mg (36.3% yield) to 5b.

Reference： [1]Location in patent: experimental part Xu, Qinyuan; Huang, Li; Liu, Juan; Ma, Liang; Chen, Tao; Chen, Jinying; Peng, Fei; Cao, Dong; Yang, Zhuang; Qiu, Neng; Qiu, Jingxiang; Wang, Guangcheng; Liang, Xiaolin; Peng, Aihua; Xiang, Mingli; Wei, Yuquan; Chen, Lijuan [European Journal of Medicinal Chemistry, 2012, vol. 52, p. 70 - 81]

29
[ 30709-67-2 ]
[ 3878-55-5 ]
[ 905405-17-6 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In chloroform; for 24h;	General procedure: A mixture of 4-(2-chlorophenyl)thiazol-2-amine (500 mg, 2.37 mmol), DMAP (13.27 mg, 0.12 mmol), EDCI (682.43 mg, 3.55 mmol) and 4-methoxy-4-oxobutanoic acid (470.3 mg, 3.55 mmol) in chloroform (20 mL) was stirred at room temperature for 24 h. The solution was filtered, and filtrate was washed with water. The organic phase was dried (Na2SO4) and evaporated to dryness. The residue was purified by flash chromatography over silica gel eluting with CH2Cl2:EtOAC (80:1) yielded 280 mg (36.3% yield) to 5b.

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 52,p. 70 - 81

30
[ 3878-55-5 ]
[ 21344-90-1 ]
[ 1376447-20-9 ]

Yield	Reaction Conditions	Operation in experiment
36.3%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In chloroform; for 24h;	General procedure: A mixture of <strong>[21344-90-1]4-(2-chlorophenyl)thiazol-2-amine</strong> (500 mg, 2.37 mmol), DMAP (13.27 mg, 0.12 mmol), EDCI (682.43 mg, 3.55 mmol) and 4-methoxy-4-oxobutanoic acid (470.3 mg, 3.55 mmol) in chloroform (20 mL) was stirred at room temperature for 24 h. The solution was filtered, and filtrate was washed with water. The organic phase was dried (Na2SO4) and evaporated to dryness. The residue was purified by flash chromatography over silica gel eluting with CH2Cl2:EtOAC (80:1) yielded 280 mg (36.3percent yield) to 5b.

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 52,p. 70 - 81

31
[ 3878-55-5 ]
[ 39893-80-6 ]
[ 1398574-78-1 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In chloroform; for 24h;	General procedure: A mixture of 4-(2-chlorophenyl)thiazol-2-amine (500 mg, 2.37 mmol), DMAP (13.27 mg, 0.12 mmol), EDCI (682.43 mg, 3.55 mmol) and 4-methoxy-4-oxobutanoic acid (470.3 mg, 3.55 mmol) in chloroform (20 mL) was stirred at room temperature for 24 h. The solution was filtered, and filtrate was washed with water. The organic phase was dried (Na2SO4) and evaporated to dryness. The residue was purified by flash chromatography over silica gel eluting with CH2Cl2:EtOAC (80:1) yielded 280 mg (36.3percent yield) to 5b.

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 52,p. 70 - 81

32
[ 3878-55-5 ]
[ 105512-79-6 ]
[ 1398574-76-9 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In chloroform for 24h;	5.1.3. General procedure for the synthesis of methyl 4-(4-(2-chlorophenyl)thiazol-2-yla-mino)-4-oxobutanoate General procedure: A mixture of 4-(2-chlorophenyl)thiazol-2-amine (500 mg, 2.37 mmol), DMAP (13.27 mg, 0.12 mmol), EDCI (682.43 mg, 3.55 mmol) and 4-methoxy-4-oxobutanoic acid (470.3 mg, 3.55 mmol) in chloroform (20 mL) was stirred at room temperature for 24 h. The solution was filtered, and filtrate was washed with water. The organic phase was dried (Na2SO4) and evaporated to dryness. The residue was purified by flash chromatography over silica gel eluting with CH2Cl2:EtOAC (80:1) yielded 280 mg (36.3% yield) to 5b.

33
[ 3878-55-5 ]
[ 5824-40-8 ]
[ 1195771-44-8 ]

Yield	Reaction Conditions	Operation in experiment
	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; In acetonitrile; at 20℃; for 24h;pH 9 - 11;	To a solution of mono-methyl hydrogen succinate (2, 45mmol) in acetonitrile (50ml) triphenylmethylamine (45mmol) and HBTU (45mmol) were added which was followed by the addition of triethylamine (90mmol). The mixture was stirred at room temperature for 24 h. The pH of the reaction mixture was kept between pH 9 and 11, and adjusted, if necessary, by the addition of triethylamine. After the reaction was completed, the volatile products were evaporated. The resulting oil was dissolved in ethyl acetate (100ml) and washed with 5percent NaHCO3 (2.x.50 ml), brine (50ml), 5percent KHSO4 (2.x.50 ml), brine (50ml) and dried over MgSO4. The solution was filtered and evaporated to dryness. The product was purified using SilicaGel column chromatography.Compound 3, methyl 4-oxo-4-(tritylamino)butanoate: Yield: 30percent; white solid, mp 157oC; Rf = 0.58 (CHCl3:AcOEt/4:1, v:v); HRMS m/z 396.1576/396.1594 (M+Na)+; 1H NMR (300MHz, CDCl3, ppm): delta 2.45-2.72 (m, 4H, 2.x.CH2), 3.65 (s, 3H, CH3), 6.83 (s, 1H, NH), 7.15-7.36 (m, 15H, Ar-H).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 5574 - 5578

34
[ 3878-55-5 ]
[ 1744-22-5 ]
[ 1394929-73-7 ]

Yield	Reaction Conditions	Operation in experiment
77%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; for 96h;	General procedure: 6-Trifluoromethoxy-benzothiazol-2-ylamine (1, 100 mg, 0.42 mmol), a carboxylic acid (0.43 mmol), and EDCI (123 mg, 0.65 mmol) were combined in methylene chloride (5 mL) and stirred 4 days. The reaction was washed with 0.1 N HCl (2 × 10 mL), dried over magnesium sulfate, filtered, and then concentrated. Chromatography on silica gel afforded compounds 20, and 21. Compound 21 was dissolved in dichloromethane and trifluoroacetic acid (1:1). After stirring 2 h the solvents were removed in vacuo to yield compound 19.

Reference： [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 5642 - 5648

35
[ 3878-55-5 ]
[ 30913-86-1 ]

Reference： [1]Chinese Journal of Chemistry,2013,vol. 31,p. 1144 - 1152

36
[ 3878-55-5 ]
[ 106-40-1 ]
[ 41167-74-2 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 100℃; for 0.5h;

Reference： [1]Kumar, Padam Praveen; Reddy, Y. Dathu; Kumari, Y. Bharathi; Devi, B. Rama; Dubey [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2014, vol. 53, # 4, p. 392 - 398]

37
[ 108-31-6 ]
[ 67-56-1 ]
[ 3878-55-5 ]
[ 3052-50-4 ]
[ 106-65-0 ]

Yield	Reaction Conditions	Operation in experiment
1: 32.9 %Chromat. 2: 12.48 %Chromat. 3: 8.07 %Chromat.	With palladium on activated charcoal; hydrogen at 190℃; Autoclave;	3 50g, 0.5 mol maleic anhydride, 49g, 1.53 mol, 3 eqv methanol, 1g, equivalent to 0.32g, 0.6 wt% palladium-carbon paste were charged to the autoclave. The vessel was sealed and then pressurised to 300 psig with hydrogen and heated to 190°C. The internal temperature of the vessel was recorded with time and, to ensure that any exotherm above the desired maximum temperature was monitored, the cooling system was turned off. The results indicated that, although the rate of temperature increase did go up, the temperature did not exceed the maximum operating parameter. Analysis of the product showed significant conversion of the maleate species to succinate with (methanol free) selectivity to mono methyl maleate and mono maleate succinate of 7.28 mol % and 1 1.08 mol % respectively. Selectivity to di-methyl maleate and dimethyl succinate were 3.59 mol% and 26.41 mol% respectively. The results are set out in the following table.

Reference： [1]Current Patent Assignee: JOHNSON MATTHEY PLC - WO2015/55992, 2015, A1 Location in patent: Page/Page column 11; 12

38
[ 3878-55-5 ]
[ 58483-95-7 ]
2-chloro-5-(3-(3-methoxy-3-oxopropyl)ureido)isonicotinic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 4-methoxy-4-oxobutanoic acid (9.7 g, 73.5 mmol) in toluene (368 mL) was added diphenylphosphoryl azide (20.2 g, 73.5 mmol) followed by TEA (12.4 g, 122.7 mmol). The reaction was stirred at RT for 30 min then <strong>[58483-95-7]5-amino-2-chloroisonicotinic acid</strong> (8.47 g, 49 mmol) was added. The reaction was heated at reflux for 6 h, cooled to RT then diluted with EA (300 mL). The mixture was washed with brine (300 mL) and out of the organic layer precipitated a solid which was filtered. The separated aqueous layer was acidified to PH 5 by adding aq. 2N HC1 and a precipitate formed. The solid was filtered and combined with the organic layer solid. The combined solids were dried to give 2-chloro-5-(3-(3-methoxy-3-oxopropyl)ureido) isonicotinic acid (26 g, >100percent yield) as brown semi-solid. LCMS: MH+ 302 MH+ and TR = 2.752 min. Used without further purification.

Reference： [1]Patent: WO2016/23825,2016,A1 .Location in patent: Page/Page column 33; 34

39
[ 3878-55-5 ]
[ 52833-94-0 ]
5-bromo-2-(3-(3-methoxy-3-oxopropyl)ureido)nicotinic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39.3%		To a solution of 4-methoxy-4-oxobutanoic acid (14.6 g, 1 10.6 mmol) in toluene (530 mL) was added diphenylphosphoryl azide (30.4 g, 110.5 mmol) followed by triethylamine (18.3 g, 181.2 mmol). The reaction was stirred at RT for 30 min then <strong>[52833-94-0]2-amino-5-bromonicotinic acid</strong> (15.9 g, 73.61 mmol) was added. The reaction was refluxed for 6 h, cooled to RT then diluted with EA (530 mL) and washed with brine (2x300 mL). The combined aqueous layers were acidified to PH 5 by adding aq. 2N HCl and a solid formed which was filtered off. The solid was dried to give 5-bromo-2-(3-(3-methoxy-3-oxopropyl)ureido)nicotinic acid (15 g, 39.3percent yield) as pale yellow solid. LCMS: MH 347 and TR = 1.047 min. Used without further purification.

Reference： [1]Patent: WO2016/23830,2016,A1 .Location in patent: Page/Page column 60; 61

40
[ 3878-55-5 ]
[ 4684-12-2 ]
C₁₅H₁₄ClNO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃; for 12h; Cooling with ice;	1A Synthesis of Compound IV-1 3.54g (20 mmol)Compound II-1 and 2.64 g (20 mmol) of compound III was dissolved in 50 mL dryTHF, cooled in an ice water bath with stirring, was added dicyclohexylcarbodiimide (DCC) 4.13 g (20 mmol ) and 4-dimethylaminopyridine (DMAP) 0.61 g(5 mmol), followed by stirring at room temperature until the reaction wascomplete by TLC (12h or less). The reaction mixture was poured into 300 mL ofice water, stirring, 100 mL × 3 of CH 2 Cl 2 the combined extracts combined,washed sequentially using 100 mL 1% brine and diluted hydrochloric acid 100 mL5%, and dried over anhydrous sodium sulfate . The desiccant was removed bysuction, and the filtrate evaporated to dryness on a rotary evaporator, theresidue was purified by column chromatography using, to give compound IV-1, awhite solid.
	With dmap; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃; Cooling with ice;	1.A Synthesis of Compound IV-1 3.54g (20 mmol) Compound II-1 and 2.64 g (20 mmol) of compound III was dissolved in 50 mL dry THF, cooled in an ice water bath with stirring, was added dicyclohexyl carbodiimide (DCC) 4.13 g (20 mmol ) and 4-dimethylaminopyridine (DMAP) 0.61 g (5 mmol), followed by stirring at room temperature until the reaction was complete by TLC (12h or less). The reaction mixture was poured into 300 mL of ice water, stirring, 100 mL × 3 of CH 2 Cl 2 the combined extracts combined, washed sequentially using 100 mL 1% brine and diluted hydrochloric acid 100 mL 5%, and dried over anhydrous sodium sulfate . The desiccant was removed by suction, and the filtrate evaporated to dryness on a rotary evaporator, the residue was purified by column chromatography using, to give compound IV-1, a white solid,

Reference： [1]Current Patent Assignee: ZHANG YUANQIANG - CN104311441, 2016, B Location in patent: Paragraph 0024-0027
[2]Current Patent Assignee: ZHANG YUANQIANG - CN104311442, 2016, B Location in patent: Paragraph 0033-0036

41
[ 3878-55-5 ]
[ 5557-81-3 ]
methyl (S)-4-((1-(benzyloxy)-1-oxopropan-2-yl)amino)-4-oxobutanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%		DIPEA (17 mL, 17 mmol) was added dropwise to a stirred suspension of L-Ala-OBn-HCl (6.02 g, 27.9 mmol) in dichloromethane (70 mL) at room temperature under an atmosphere of nitrogen. On dissolution, the solution was cooled to 0 C and succinic acid monomethyl ester (4.05 g, 30.7 mmol) and 1 -hydroxybenzotriazole (4.52 g, 33.48 mmol) were added successively, each in one portion. The suspension was stirred at 0 C for a further 15 min, and then DCC (6.91 g, 33.48 mmol) was added in one portion. The mixture was allowed to warm to room temperature over the course of 18 h and then filtered, and the filtrate was evaporated in vacuo. The residue was taken up in ethyl acetate and filtered, and the filtrate was then washed with 10% aqueous citric acid solution followed by saturated aqueous sodium bicarbonate solution. The combined organic extracts were dried and evaporated in vacuo to leave the crude product which was purified by chromatography on silica using 3 :2 petroleum ether-EtOAc as eluent to give the dipeptide 15 (7.2 g, 24.55 mmol) as a white solid in 88% yield. [a]D20 - 4.3 (c 1.0, CHC13).
88%		DIPEA (17 mL, 17 mmol) was added dropwise to a stirred suspension of L-Ala-OBn·HCl (6.02 g, 27.9 mmol) in dichloromethane (70 mL) at room temperature under an atmosphere of nitrogen. On dissolution, the solution was cooled to 0 C and succinic acid monomethyl ester (4.05 g, 30.7 mmol) and 1-hydroxybenzotriazole (4.52 g, 33.48 mmol) were added successively, each in one portion. The suspension was stirred at 0 C for a further 15 min, and then DCC (6.91 g, 33.48 mmol) was added in one portion. The mixture was warmed to room temperature in 18 h and then filtered, and the filtrate was evaporated in vacuo. The residue was taken up in ethyl acetate and filtered, and the filtrate was then washed with 10% aqueous citric acid solution followed by saturated aqueous sodium bicarbonate solution. The combined organic layers were dried and evaporated in vacuo to afford the crude product which was purified by chromatography on silica using 3:2 petroleum ether-EtOAc as eluent to yield 6 (7.2 g, 24.55 mmol, 88%) as a white solid. [alpha]D 20 - 4.3 (c 1.0, CHCl3). 1H NMR (300 MHz, CDCl3) delta 7.30-7.20 (m, 5H), 6.36 (s, 1H), 5.08 (dd, J=18, 12 Hz, 2H), 4.54 (p, J = 7.2 Hz, 1H), 3.58 (s, 1H), 2.66-2.54 (m, 2H). 2.50-2.4 (m, 2H), 1.32 (d, J = 7.2 Hz, 1H). 13C NMR (75 MHz, CDCl3) delta 173.3, 172.9, 171.0, 135.4, 128.6, 128.4, 128.1, 67.1, 51.8, 48.2, 30.8, 29.2, 18.3. HRMS (ESI) calc for C15H20NO5 +: 294.1336 [M+H]+; found: 294.1340

Reference： [1]Patent: WO2017/5879,2017,A1 .Location in patent: Page/Page column 19; 20
[2]Free Radical Biology and Medicine,2018,vol. 126,p. 101 - 112

42
[ 3878-55-5 ]
[ 4523-45-9 ]
C₁₆H₁₇NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; dicyclohexyl-carbodiimide; In tetrahydrofuran; at 20℃; for 12h;Cooling with ice;	3.14 g (20 mmol) of compound II-1 and 2.64 g (20 mmol) Compound III was dissolved in 50 mL of dry THF, stirred under ice-cooling in an ice bath,A solution of 4.13 g (20 mmol) of dicyclohexylcarbodiimide (DCC)And 0.61 g (5 mmol) of 4-dimethylaminopyridine (DMAP) were added, followed by stirring at room temperature,Until the TLC detection reaction is completed (within 12 h). The reaction mixture was poured into 300 mL of ice water,Stirred, extracted with 100 mL x 3 CH2Cl2, combined with the extracted phase,Washed sequentially with 100 mL of 1% dilute hydrochloric acid and 100 mL of 5% brine,Dried over anhydrous sodium sulfate. The desiccant was removed by suction filtration, and the filtrate was evaporated to dryness on a rotary evaporator,The resulting residue was purified by column chromatography to give compound IV-1 as a white solid.

Reference： [1]Patent: CN104311445,2016,B .Location in patent: Paragraph 0032-0035

43
[ 878671-94-4 ]
[ 3878-55-5 ]
C₁₈H₁₉NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; dicyclohexyl-carbodiimide; In tetrahydrofuran; at 20℃; for 12h;Cooling with ice;	3.66 g (20 mmol) of compound II-2 and 2.64 g (20 mmol)Compound III was dissolved in 50 mL of dry THF, stirred under ice-cooling in an ice bath,A solution of 4.13 g (20 mmol) of dicyclohexylcarbodiimide (DCC)And 0.61 g (5 mmol) of 4-dimethylaminopyridine (DMAP) were added, followed by stirring at room temperature,Until the TLC detection reaction is completed (within 12 h). The reaction mixture was poured into 300 mL of ice water,Stirred, extracted with 100 mL x 3 CH2Cl2, combined with the extracted phase,Washed sequentially with 100 mL of 1% dilute hydrochloric acid and 100 mL of 5% brine,Dried over anhydrous sodium sulfate. The desiccant was removed by suction filtration,The filtrate was evaporated to dryness on a rotary evaporator and the resulting residue was purified by column chromatography to give compound IV-2.

Reference： [1]Patent: CN104311445,2016,B .Location in patent: Paragraph 0041-0044

44
[ 3878-55-5 ]
[ 776-34-1 ]
C₁₅H₁₄N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; dicyclohexyl-carbodiimide; In tetrahydrofuran; at 20℃;Cooling with ice;	3.76 g (20 mmol) of compound II-1 and 2.64 g (20 mmol) of compound III were dissolved in 50 mL of dry THF,(20 mmol) of dicyclohexylcarbodiimide (DCC) and 0.61 g (5 mmol) of 4-dimethylaminopyridine (DMAP) were added under ice-cooling,And then stirred at room temperature until the TLC detection reaction is completed (within 12 h).The reaction mixture was poured into 300 mL of ice water, stirred, extracted with 100 mL x 3 CH2Cl2, the combined phases were combined,Washed sequentially with 100 mL of 1% dilute hydrochloric acid and 100 mL of 5% brine,Dried over anhydrous sodium sulfate. The desiccant was removed by suction filtration, and the filtrate was evaporated to dryness on a rotary evaporator,The resulting residue was purified by column chromatography to give compound IV-1 as a white solid,

Reference： [1]Patent: CN104311444,2016,B .Location in patent: Paragraph 0028; 0029; 0030; 0031

45
[ 3878-55-5 ]
[ 85342-65-0 ]
C₁₃H₇Cl₄NO₆ [ No CAS ]

Reference： [1]Nature,2017,vol. 545,p. 213 - 218

46
[ 3878-55-5 ]
[ 90-34-6 ]
methyl 3-({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)propanoate [ No CAS ]

Reference： [1]ChemistryOpen,2018,vol. 7,p. 624 - 638
[2]Molecules,2018,vol. 23

47
[ 3878-55-5 ]
[ 2140-46-7 ]
(3S,8S,9S,10R,13R,14S,17R)-17-((R)-6-hydroxy-6-methylheptan-2-yl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl methyl succinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23%	With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; for 15h;	[0176] To a stirred solution of 4-methoxy-4-oxobutanoic acid (65 mg, 0.496 mmol) in DCM (5 mL) was added DMAP (90 mg, 0.744 mmol), DCC (153 mg, 0.744 mmol) followed by addition of a solution of 25-hydroxy cholesterol 1 (100 mg, 0.248 mmol) in DCM (2 mL). The resulting reaction mass was stirred at RT for 15h. After completion of reaction (TLCmonitoring), the reaction mixture was filtered through Celite pad and washed with 50% EtOAc in hexane. The filtrate was washed with 5% citric acid (10 mL), saturated solution of NaHC03 (10 mL) and water (10 mL) sequentially. The organic layer was dried over anhydrous Na2S04, filtered and concentrated under reduced pressure to get crude. The crude was purified over flash column (Silica l2g, Redisep), eluted with a gradient of 0-30% EtOAc in hexane and run time of 40 min to get desired product 1.19 (30 mg, Yield: 23%) as off white solid. 1H-NMR (400 MHz, DMSO-de): d 5.37 (s, 1H), 4.62 (t, J=8 Hz, 1H), 3.69 (s, 3H), 2.61 (s, 4H), 2.32(d, J=8 Hz, 2H), 1.84-2.02 (m, 5H) and 1.04-1.53 (m, 36H). LCMS: 534 (M+H+l7)+, 99.01%.

Reference： [1]Patent: WO2019/108673,2019,A1 .Location in patent: Paragraph 0176

48
[ 3878-55-5 ]
[ 140-11-4 ]
[ 53314-75-3 ]

Yield	Reaction Conditions	Operation in experiment
33%	With 1,1'-carbonyldiimidazole; lithium diisopropyl amide In tetrahydrofuran; hexane at -70 - 25℃; Inert atmosphere;	108.1 Step 1: Synthesis of 1-benzyl 6-methyl 3-oxohexanedioate To a stirred solution of butane- 1,4-dioic acid monomethyl ester (10.0 g, 75.8 mmol, 1.0 equiv) in IMF (100 mL) was added GDI (12.3 g, 75.8 mmol, 1.0 equiv). The mixture was stirred for 10 min at 25 degrees C to make solution A. Into a 1 L 3-necked round-bottom flask were added LDA (110 mL, 219 mmol, 2.06 equiv, 2 M solution in Ti ll' hexane; in THF (100 mL) and BnOAc (20.5 g, 136.4 mmol, 1.8 equiv) dropwise at -70 degrees C. The resulting mixture was stirred for 5 min at -70 degrees C under nitrogen atmosphere. To the above mixture was added solution A dropwise at -70 degrees C. The resulting mixture was stirred for an additional 5 min at -70 degrees C. The mixture was allowed to warm to 25 degrees C and quenched with water (100 mL). The resulting mixture was extracted with EtOAe (3x300 mL). The combined organic layers were washed with brine (200 mL), and dried over anhydrous NaiSQi. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE/EtOAc (5: 1) to afford the product as 1 -benzyl 6-methyl 3- oxohexanedioate (7 g, 33%) as a light yellow oil. MS: (ES, m/z): 265 [M+H]+.
	With 1,1'-carbonyldiimidazole; lithium diisopropyl amide	65 Example 65 Example 65 Synthesis of 1-benzyl 6-methyl 3-oxohexanedioate. To a solution of benzyl acetate (1.5 g, 10 mmol) in THF(10 mL) was added LDA (1 M, 15 mmol) at -78° C. and stirred for 1 h (solution A). To a solution of 4-methoxy-4-oxobutanoic acid (1.58 g, 12 mmol) in THF (10 mL) was added CDI (1.94 g, 12 mmol) and stirred at RT for 30 min (solution B). Solution B was added to solution A at -78° C. and stirred for another 2 h. Saturated NH4Cl(100 mL) was added to quenched the reaction and the reaction mixture was extracted with EtOAc (100 mL*3). The combined organics were concentrated and purified by silica gel chromatography (EA/PE=1/10) to give 1-benzyl 6-methyl 3-oxohexanedioate (500 mg, yield: 19%) as a colorless oil. ESI-MS [M+H]+: 265.1.
	With 1,1'-carbonyldiimidazole; lithium diisopropyl amide	82 Example 82 Example 82 Synthesis of 1-benzyl 6-methyl 3-oxohexanedioate. To a solution of benzyl acetate (1.5 g, 10 mmol) in THF (10 mL) was added LDA (1 M, 15 mmol) at -78° C. and stirred for 1 h (solution A). To a solution of 4-methoxy-4-oxobutanoic acid (1.58 g, 12 mmol) in THF (10 mL) was added CDI (1.94 g, 12 mmol) and stirred at RT for 30 min (solution B). Solution B was added to solution A at -78° C. and stirred for another 2 h. Saturated NH4Cl (100 mL) was added to quenched the reaction and the reaction mixture was extracted with EtOAc (100 mL*3). The combined organics were concentrated and purified by silica gel chromatography (EA/PE=1/10) to give 1-benzyl 6-methyl 3-oxohexanedioate (500 mg, yield: 19%) as a colorless oil. ESI-MS [M+H]+: 265.1.

Reference： [1]Current Patent Assignee: COMET THERAPEUTICS - WO2020/113209, 2020, A1 Location in patent: Paragraph 2121
[2]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US2019/284182, 2019, A1
[3]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US2019/284182, 2019, A1

49
[ 3878-55-5 ]
[ 360-03-2 ]
C₁₂H₁₂F₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%	With 2,4,6-trimethyl-pyridine; tetrabutylammonium perchlorate; silver perchlorate In dichloromethane at 20℃; for 3h; Electrolysis; Molecular sieve;

Reference： [1]Xiang, Jinbao; Shang, Ming; Kawamata, Yu; Lundberg, Helena; Reisberg, Solomon H.; Chen, Miao; Mykhailiuk, Pavel; Beutner, Gregory; Collins, Michael R.; Davies, Alyn; Del Bel, Matthew; Gallego, Gary M.; Spangler, Jillian E.; Starr, Jeremy; Yang, Shouliang; Blackmond, Donna G.; Baran, Phil S. [Nature, 2019, vol. 573, # 7774, p. 398 - 402]

50
[ 3878-55-5 ]
[ 1416881-52-1 ]
[ 2766554-80-5 ]

Yield	Reaction Conditions	Operation in experiment
40%	With caesium carbonate In dimethyl sulfoxide Inert atmosphere; Irradiation;

Reference： [1]Grotjahn, Sascha; König, Burkhard [Organic Letters, 2021, vol. 23, # 8, p. 3146 - 3150]

51
[ 108-94-1 ]
[ 110-94-1 ]
[ 124-04-9 ]
[ 627-93-0 ]
[ 3878-55-5 ]
[ 110-15-6 ]
[ 13984-57-1 ]
[ 627-91-8 ]
[ 626-86-8 ]
[ 6938-94-9 ]
[ 103-23-1 ]
[ 3128-06-1 ]
bis(1-methylpropyl) 2,2-dimethylpentanedioate [ No CAS ]
[ 123-76-2 ]
[ 539-88-8 ]
[ 123-25-1 ]
[ 106-65-0 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: cyclohexanone With 7K⁽¹⁺⁾*P₂Mo₅VW₁₂O₆₂^(7-) at 90℃; Stage #2: With dihydrogen peroxide at 90℃; for 20h;	2.2 Catalytic test General procedure: The synthesis method based on the one described inthe literature24 has already been used in our previouswork.22,23 The liquid phase oxidation of cyclohexanone(-one) or the mixture of cyclohexanone (-one)and cyclohexanol (-ol) was carried out at 90 C, usinga 100 mL round-bottom flask equipped with a magneticstirring bar and a reflux condenser. The reactionmixture, consisting of a calculated amount of catalystand substrate, was stirred at 800 rpm; after thereduction of POM, which is manifested by a colourchange from yellow or light green to blue, hydrogenperoxide (30%) was then added dropwise until theinitial colour of POM reappeared. The POM, which isin its oxidized form (yellow or light green colour),continues to oxidize the substrate and after its reduction(blue colour), peroxide is then added dropwiseand so on. The end of the reaction was estimated whenthe catalyst was no longer being reduced. The reactiontime was found to be 20 h. It should be noted that above 90 C, hydrogen peroxide can rapidlydecompose.

Reference： [1]Dermeche, Leila; Idrissou, Yasmina; Mazari, Tassadit; Moudjahed, Mohammed; Rabia, Cherifa [Journal of Chemical Sciences, 2022, vol. 134, # 1]

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P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 3878-55-5 ] {[proInfo.proName]}

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[ 3878-55-5 ] Synthesis Path-Upstream 1~6

[ 3878-55-5 ] Synthesis Path-Downstream 1~51

Similar Product of [ 3878-55-5 ]

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Aliphatic Chain Hydrocarbons

Esters

Carboxylic Acids

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[ 3878-55-5 ]

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