Home Cart 0 Sign in  
X

[ CAS No. 4755-77-5 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
HazMat Fee +

There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.

Type HazMat fee for 500 gram (Estimated)
Excepted Quantity USD 0.00
Limited Quantity USD 15-60
Inaccessible (Haz class 6.1), Domestic USD 80+
Inaccessible (Haz class 6.1), International USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic USD 100+
Accessible (Haz class 3, 4, 5 or 8), International USD 200+
3d Animation Molecule Structure of 4755-77-5
Chemical Structure| 4755-77-5
Chemical Structure| 4755-77-5
Structure of 4755-77-5 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 4755-77-5 ]

Related Doc. of [ 4755-77-5 ]

Alternatived Products of [ 4755-77-5 ]

Product Details of [ 4755-77-5 ]

CAS No. :4755-77-5 MDL No. :MFCD00000706
Formula : C4H5ClO3 Boiling Point : -
Linear Structure Formula :C2H5OC(O)C(O)Cl InChI Key :OWZFULPEVHKEKS-UHFFFAOYSA-N
M.W : 136.53 Pubchem ID :20884
Synonyms :

Calculated chemistry of [ 4755-77-5 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 8
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.5
Num. rotatable bonds : 3
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 27.62
TPSA : 43.37 Ų

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) : -6.12 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.49
Log Po/w (XLOGP3) : 1.43
Log Po/w (WLOGP) : 0.31
Log Po/w (MLOGP) : -0.09
Log Po/w (SILICOS-IT) : 0.64
Consensus Log Po/w : 0.76

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.39
Solubility : 5.57 mg/ml ; 0.0408 mol/l
Class : Very soluble
Log S (Ali) : -1.95
Solubility : 1.55 mg/ml ; 0.0113 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -0.9
Solubility : 17.4 mg/ml ; 0.127 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.65

Safety of [ 4755-77-5 ]

Signal Word:Danger Class:8,3
Precautionary Statements:P280-P305+P351+P338-P310 UN#:2920
Hazard Statements:H226-H314 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 4755-77-5 ]

* 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 [ 4755-77-5 ]
  • Downstream synthetic route of [ 4755-77-5 ]

[ 4755-77-5 ] Synthesis Path-Upstream   1~51

  • 1
  • [ 188290-36-0 ]
  • [ 4755-77-5 ]
  • [ 4075-59-6 ]
  • [ 4075-58-5 ]
Reference: [1] Justus Liebigs Annalen der Chemie, 1924, vol. 437, p. 25,31, 32
  • 2
  • [ 79-19-6 ]
  • [ 4755-77-5 ]
  • [ 64837-53-2 ]
YieldReaction ConditionsOperation in experiment
24% at 70℃; for 5 h; Step 1 ethyl 5-amino-l,3,4-thiadiazole-2-carboxylate To a solution of hydrazinecarbothioamide (10 g, 54.8 mmol) in POCI3 (25 mL) was added ethyl 2-chloro-2-oxacetate (6.1 mL, 54.8 mmol). The reaction was heated to 70°C and stirred for 5 h. POCI3 was completely removed from the reaction mixture under vacuum. The residue was diluted with ice cold water (150 mL) and basified to pH 8 with saturated sodium bicarbonate solution and then extracted with ethyl acetate (200 mL). The organic layer was separated and dried over a2S04, and the solvent was evaporated to obtain crude product. The crude product was purified by flash chromatography (silica gel 100-200?, 2percent methanol and dichloromethane) to afford ethyl 5-amino-l,3,4-thiadiazole-2-carboxylate as a yellow solid (3.1 g, 24percent yield). ? NMR (400 MHz, DMSO-d6): ? 7.94 (s, 2H), 4.29 (q, 2H), 1.27 (t, 3H); LC- MS m/z calcd for [M+H]+ 174.03, found 174.1.
Reference: [1] Patent: WO2013/49565, 2013, A1, . Location in patent: Page/Page column 68
[2] Annali di Chimica (Rome, Italy), 1959, vol. 49, p. 2124,2131
[3] Patent: WO2007/38865, 2007, A1, . Location in patent: Page/Page column 47
  • 3
  • [ 4755-77-5 ]
  • [ 79476-04-3 ]
  • [ 4491-33-2 ]
Reference: [1] Chemical and Pharmaceutical Bulletin, 1995, vol. 43, # 6, p. 1028 - 1030
  • 4
  • [ 5468-37-1 ]
  • [ 4755-77-5 ]
  • [ 13575-16-1 ]
YieldReaction ConditionsOperation in experiment
22%
Stage #1: With triethylamine In dichloromethane at 0 - 20℃; for 22 h;
Stage #2: for 4 h; Reflux
INTERMEDIATE 51 - PREPARATION OF Ethyl 5-phenyloxazole-2-carboxylate. ; Triethylamine (1.08 mL; 7.69 mmol) was added to a mixture of 2-amino-1-phenylethanone hydrochloride (0.550 g; 3.08 mmol) and ethyl 2-chloro-2-oxoacetate (0.369 mL; 3.23 mmol) in dichloromethane (10 ml.) at 00C. The reaction mixture was then stirred at room temperature for 22 hand diluted with dichloromethane (40 ml_). The organic layer was washed successively with a saturated aqueous solution of sodium carbonate, and water. The organic layer was dried over magnesium sulfate and was concentrated under reduced pressure. The crude residue was dissolved in phosphorus (V) oxychloride (10 ml) and the solution was refluxed for 4 hours. After cooling, the volatiles were removed under reduced pressure and the residue was dissolved in dichloromethane. The organic layer was then carefully washed with a saturated aqueous solution of sodium carbonate, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent 15 to 100percent dichloromethane in heptane) to afford 0.146 g (22percent overall yield) of ethyl 5-phenyloxazole-2-carboxylate as a solid. ESI/APCI(+) : 218 (M+H), 240 (M+Na).
Reference: [1] Patent: WO2010/142801, 2010, A1, . Location in patent: Page/Page column 161-162
  • 5
  • [ 4755-77-5 ]
  • [ 15658-60-3 ]
Reference: [1] Chemical and Pharmaceutical Bulletin, 1995, vol. 43, # 6, p. 1028 - 1030
[2] Chemical and Pharmaceutical Bulletin, 1995, vol. 43, # 6, p. 1028 - 1030
  • 6
  • [ 4755-77-5 ]
  • [ 15658-60-3 ]
Reference: [1] Chemical and Pharmaceutical Bulletin, 1995, vol. 43, # 6, p. 1028 - 1030
  • 7
  • [ 95-92-1 ]
  • [ 4755-77-5 ]
YieldReaction ConditionsOperation in experiment
12.22 g
Stage #1: With potassium acetate In water at 70 - 80℃; for 2 h;
Stage #2: With thionyl chloride In diethyl ether for 15 h; Cooling with ice; Reflux
A mixture of potassium acetate (20 g), water (30 ml) and diethyl oxalate (29.2 g, 0.2 mol) was stirred at 70-80 °C for 2 h. The reaction mixture was cooled and condensed to 30 ml. After ethanol (50 ml) and diethyl ether (150 ml) were added, the solution was filtrated to give 23.61 g of potassium monoethyl oxalate (76percent). SOCl2 (30 g, 0.25 mol) was added slowly to this dry potassium salt (20.6 g, 0.13 mol) previously mixed with diethyl ether (20 ml) in an ice bath. The mixture was then heated under reflux for 15 h. The white solid of produced potassium chloride was filtrated, the filtrate was fractionated and a fraction of 125-130 °C was collected to give 12.22 g of 8 (69percent).
Reference: [1] Gazzetta Chimica Italiana, 1891, vol. 21 I, p. 306
[2] Monatshefte fuer Chemie, 1905, vol. 26, p. 375
[3] Chemische Berichte, 1886, vol. 19, p. 2159[4] Justus Liebigs Annalen der Chemie, 1889, vol. 254, p. 27
[5] Recueil des Travaux Chimiques des Pays-Bas, 1907, vol. 26, p. 381
[6] Chemische Berichte, 1943, vol. 76, p. 310,311
[7] DRP/DRBP Org.Chem.,
[8] Bulletin de la Societe Chimique de France, 1927, vol. <4>41, p. 47
[9] Bulletin de la Societe Chimique de France, 1925, vol. <4> 37, p. 1398[10] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1923, vol. 177, p. 452
[11] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 12, p. 3865 - 3872
  • 8
  • [ 1906-57-6 ]
  • [ 4755-77-5 ]
Reference: [1] Organic and Biomolecular Chemistry, 2011, vol. 9, # 8, p. 2702 - 2714
[2] Journal of Organic Chemistry, 1968, vol. 33, # 10, p. 3980 - 3983
  • 9
  • [ 79-37-8 ]
  • [ 64-17-5 ]
  • [ 4755-77-5 ]
Reference: [1] Chemical Communications, 2012, vol. 48, # 25, p. 3133 - 3135
[2] Chinese Journal of Chemistry, 2010, vol. 28, # 3, p. 475 - 479
[3] Advanced Synthesis and Catalysis, 2015, vol. 357, # 18, p. 3943 - 3948
[4] Journal of the American Chemical Society, 1963, vol. 85, p. 585 - 591
[5] Tetrahedron, 1993, vol. 49, # 36, p. 8241 - 8256
[6] Bulletin of the Chemical Society of Japan, 1991, vol. 64, # 1, p. 57 - 67
[7] European Journal of Organic Chemistry, 2001, # 3, p. 545 - 552
[8] Journal of Agricultural and Food Chemistry, 2008, vol. 56, # 16, p. 7326 - 7332
[9] Journal of Agricultural and Food Chemistry, 2011, vol. 59, # 23, p. 12543 - 12549
  • 10
  • [ 617-37-8 ]
  • [ 4755-77-5 ]
Reference: [1] Chemische Berichte, 1904, vol. 37, p. 3679
[2] Bulletin de la Societe Chimique de France, 1927, vol. <4>41, p. 539[3] Bulletin de la Societe Chimique de France, 1928, vol. 43, p. 860
[4] Recueil des Travaux Chimiques des Pays-Bas, 1907, vol. 26, p. 381
[5] European Journal of Medicinal Chemistry, 2012, vol. 50, p. 18 - 26
  • 11
  • [ 95-92-1 ]
  • [ 75-00-3 ]
  • [ 4755-77-5 ]
Reference: [1] J. Appl. Chem. USSR (Engl. Transl.), 1982, vol. 55, # 9, p. 1893 - 1895[2] Zhurnal Prikladnoi Khimii (Sankt-Peterburg, Russian Federation), 1982, vol. 55, # 9, p. 2058 - 2061
  • 12
  • [ 86523-76-4 ]
  • [ 4755-77-5 ]
  • [ 86523-79-7 ]
Reference: [1] Journal of Medicinal Chemistry, 1987, vol. 30, # 1, p. 13 - 19
  • 13
  • [ 95-92-1 ]
  • [ 79-37-8 ]
  • [ 75-00-3 ]
  • [ 63938-37-4 ]
  • [ 98019-44-4 ]
  • [ 4755-77-5 ]
Reference: [1] J. Appl. Chem. USSR (Engl. Transl.), 1982, vol. 55, # 9, p. 1893 - 1895[2] Zhurnal Prikladnoi Khimii (Sankt-Peterburg, Russian Federation), 1982, vol. 55, # 9, p. 2058 - 2061
  • 14
  • [ 91467-21-9 ]
  • [ 91467-24-2 ]
  • [ 4755-77-5 ]
  • [ 1795-48-8 ]
Reference: [1] Journal of Organic Chemistry, 1984, vol. 49, # 20, p. 3675 - 3681
  • 15
  • [ 6957-89-7 ]
  • [ 4755-77-5 ]
Reference: [1] Bulletin de la Societe Chimique de France, 1916, vol. <4> 19, p. 17
[2] Justus Liebigs Annalen der Chemie, 1913, vol. 397, p. 363
  • 16
  • [ 79-37-8 ]
  • [ 109-92-2 ]
  • [ 6191-99-7 ]
  • [ 4755-77-5 ]
Reference: [1] Journal of Chemical Research, 2011, vol. 35, # 7, p. 416 - 419
  • 17
  • [ 90952-82-2 ]
  • [ 4755-77-5 ]
Reference: [1] J. Gen. Chem. USSR (Engl. Transl.), 1964, vol. 34, p. 610 - 613[2] Zhurnal Obshchei Khimii, 1964, vol. 34, p. 609 - 613
  • 18
  • [ 6957-89-7 ]
  • [ 75-00-3 ]
  • [ 4755-77-5 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 1984, vol. 57, # 3, p. 810 - 814
  • 19
  • [ 10026-13-8 ]
  • [ 95-92-1 ]
  • [ 4755-77-5 ]
Reference: [1] Recueil des Travaux Chimiques des Pays-Bas, 1907, vol. 26, p. 381
[2] Chemische Berichte, 1877, vol. 10, p. 2228
  • 20
  • [ 7719-09-7 ]
  • [ 617-37-8 ]
  • [ 4755-77-5 ]
Reference: [1] Chemische Berichte, 1904, vol. 37, p. 3679
  • 21
  • [ 617-37-8 ]
  • [ 10025-87-3 ]
  • [ 4755-77-5 ]
Reference: [1] Chemische Berichte, 1871, vol. 4, p. 599
  • 22
  • [ 4755-77-5 ]
  • [ 110-83-8 ]
  • [ 39183-57-8 ]
  • [ 617-36-7 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 1972, vol. 45, # 12, p. 3567 - 3571
  • 23
  • [ 64-17-5 ]
  • [ 4755-77-5 ]
  • [ 39183-52-3 ]
  • [ 617-36-7 ]
  • [ 19617-44-8 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 1972, vol. 45, # 12, p. 3567 - 3571
  • 24
  • [ 4755-77-5 ]
  • [ 67-63-0 ]
  • [ 39183-50-1 ]
  • [ 39183-53-4 ]
  • [ 617-36-7 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 1972, vol. 45, # 12, p. 3567 - 3571
  • 25
  • [ 7664-41-7 ]
  • [ 4755-77-5 ]
  • [ 617-36-7 ]
Reference: [1] Chemische Berichte, 1871, vol. 4, p. 599
  • 26
  • [ 56000-35-2 ]
  • [ 4755-77-5 ]
  • [ 62135-58-4 ]
YieldReaction ConditionsOperation in experiment
90.6% at 100℃; To a light red solution of 1,2-diaminopyridinium 2,4,6-trimethylbenzenesulfonate (10.9 g, 35.2 mmol) in pyridine (50 mL) was added ethyl 2-chloro-2-oxoacetate (9.62 g, 7.84 mL, 70.5 mmol) at RT (exotherm reaction.).
The light red solution turned into a dark red solution.
The mixture was heated to 100° C. and stirred overnight.
The reaction mixture was evaporated and the black residue was triturated for 30 min with Na2CO3 (saturated aqueous solution, 300 mL).
The reaction mixture was extracted with dichloromethane (4*250 mL) and the combined organic layer was dried over MgSO4 and concentrated in vacuo to give 6.64 g of crude product.
The crude product was suspended in diethyl ether (30 mL), filtered and washed with diethyl ether.
The obtained precipitate was dried in vacuo to give the product as light brown solid (6.1 g, 31.9 mmol, 90.6percent).
MS: M=192.2 (M+H)+
90.6% at 100℃; To a light red solution of 1,2-diaminopyridinium 2,4,6-trimethylbenzenesulfonate (10.9 g, 35.2 mmol) in pyridine (50 mL) was added ethyl 2-chloro-2-oxoacetate (9.62 g, 7.84 mL, 70.5 mmol) at RT (exotherm reaction.). The light red solution turned into a dark red solution. The mixture was heated to 100 °C and stirred overnight. The reaction mixture was evaporated and the black residue was triturated for 30 min with Na2C03 (saturated aqueous solution, 300 mL). The reaction mixture was extracted with dichloromethane (4 x 250 mL) and the combined organic layer was dried over MgS04 and concentrated in vacuo to give 6.64 g of crude product. The crude product was suspended in diethyl ether (30mL), filtered and washed with diethyl ether. The obtained precipitate was dried in vacuo to give the product as light brown solid (6.1 g, 31.9 mmol, 90.6 percent).MS: M = 192.2 (M+H)+
Reference: [1] Patent: US2013/59833, 2013, A1, . Location in patent: Paragraph 0515-0516
[2] Patent: WO2013/34506, 2013, A1, . Location in patent: Page/Page column 88
  • 27
  • [ 4755-77-5 ]
  • [ 118493-85-9 ]
  • [ 40019-21-4 ]
Reference: [1] Journal of Medicinal Chemistry, 2004, vol. 47, # 14, p. 3642 - 3657
[2] Patent: WO2007/124546, 2007, A1, . Location in patent: Page/Page column 60
  • 28
  • [ 4755-77-5 ]
  • [ 22059-22-9 ]
  • [ 40019-21-4 ]
YieldReaction ConditionsOperation in experiment
63% With pyridine In dichloromethane for 14 h; Reflux Scheme 11 : Synthesis of ethyl 3-methyl-l,2,4-oxadiazole-5-carboxylate 2.2mTo a solution of (E)-N'-hydroxyacetimidamide 2.0m (1.0 g, 13.50 mmol, 1 eq.) and pyridine (4.35 mL, 54.0 mmol, 4 eq.) in dry DCM (40 mL) was added at RT ethyloxalyl chloride (2.4 g, 18.0 mmol, 1.3 eq.). The solution was stirred at reflux for 14 hours. The reaction mixture was cooled down to RT and quenched with NH4C1 sat. (30 mL). The aqueous phase was extracted with DCM (2 x 50 mL). The organic phases were combined, washed with NaHC03 sat. (50 mL), dried over MgS04, filtered and concentrated under reduced pressure to give 2.2m as yellow oil (1.32 g, 8.45 mmol, 63 percent) which was used in the next step without further purification. LCMS: P = 92 , retention time = 2.0 min, (M+H)+: 157.
Reference: [1] Patent: WO2013/50424, 2013, A1, . Location in patent: Page/Page column 116
  • 29
  • [ 4755-77-5 ]
  • [ 118493-85-9 ]
  • [ 40019-21-4 ]
Reference: [1] Patent: US3991067, 1976, A,
  • 30
  • [ 92273-73-9 ]
  • [ 4755-77-5 ]
  • [ 5753-96-8 ]
YieldReaction ConditionsOperation in experiment
37%
Stage #1: With copper(l) iodide In tetrahydrofuran at -25 - 0℃; for 0.333333 h;
Stage #2: at -25℃; for 3 h;
A stirred solution of copper iodide (2.29 g, 12 mmol) in anhydrous tetrahydrofuran was cooled to 25° C. and slowly treated dropwise with a 0.5 M tetrahydrofuran solution of 21 (24 mL, 12 mmol). After complete addition, the reaction mixture was allowed to warm to 0° C., stirred at this temperature for 20 min, and again cooled back to 25° C. The reaction mixture was treated dropwise with 20 (1.37 g, 10 mmol) and stirred at 25° C. for 3 h. The reaction mixture was allowed to warm to room temperature, quenched with saturated aqueous ammonium chloride, and the aqueous layer was extracted with diethyl ether. The combined organics were washed with brine, filtered, dried with sodium sulfate, and concentrated in vacuo. The crude material was purified by ISCO flash column chromatography using prepacked RediSep silica gel columns (gradient elution, 0-->20percent ethyl acetate in hexanes) to afford the title compound 22 (0.60 g, 37percent) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 0.91-0.98 (3H, m), 1.34-1.47 (5H, m), 1.58-1.76 (2H, m), 2.83 (1H, t, J=7.3 Hz), 4.27-4.37 (2H, m).
Reference: [1] Patent: US2008/90814, 2008, A1, . Location in patent: Page/Page column 23-24
  • 31
  • [ 60-29-7 ]
  • [ 3431-67-2 ]
  • [ 4755-77-5 ]
  • [ 5753-96-8 ]
  • [ 42513-46-2 ]
  • [ 97834-75-8 ]
Reference: [1] Journal of the American Chemical Society, 1954, vol. 76, p. 1914
  • 32
  • [ 79-37-8 ]
  • [ 109-92-2 ]
  • [ 6191-99-7 ]
  • [ 4755-77-5 ]
Reference: [1] Journal of Chemical Research, 2011, vol. 35, # 7, p. 416 - 419
  • 33
  • [ 107-10-8 ]
  • [ 4755-77-5 ]
  • [ 16369-21-4 ]
Reference: [1] Journal of Medicinal Chemistry, 1973, vol. 16, # 6, p. 736 - 739
  • 34
  • [ 623-33-6 ]
  • [ 4755-77-5 ]
  • [ 29655-79-6 ]
YieldReaction ConditionsOperation in experiment
51% With triethylamine In dichloromethane Example 2 Ii; Compound 4 was prepared according to the Ref: J. Hetero. Chem. 1995, 32, 1693-1702. Then, it was reduced by NaBH4ZLiCl in ethanol solution. Further oxidation by Dess-Martin reagent gave the desired aldehyde 6 in 25 percent overall two-step yield.
Reference: [1] Synthetic Communications, 2000, vol. 30, # 17, p. 3171 - 3180
[2] Patent: WO2007/124546, 2007, A1, . Location in patent: Page/Page column 63
[3] Chemische Berichte, 1897, vol. 30, p. 590
[4] Journal of the American Chemical Society, 1997, vol. 119, # 1, p. 86 - 93
[5] Organic Process Research and Development, 2004, vol. 8, # 2, p. 192 - 200
  • 35
  • [ 4755-77-5 ]
  • [ 29655-79-6 ]
Reference: [1] Patent: US2002/35115, 2002, A1,
  • 36
  • [ 108-86-1 ]
  • [ 4755-77-5 ]
  • [ 7099-87-8 ]
Reference: [1] Collection of Czechoslovak Chemical Communications, 1964, vol. 29, p. 97 - 120
  • 37
  • [ 4755-77-5 ]
  • [ 108-90-7 ]
  • [ 34966-48-8 ]
YieldReaction ConditionsOperation in experiment
67% With aluminum (III) chloride In dichloromethane at 0 - 20℃; for 12 h; Step 1:
Synthesis of ethyl 2-(4-chlorophenyl)-2-oxoacetate
To a stirred solution of chlorobenzene (10 mL, 100.0 mmol) and ethyl 2-chloro-2-oxoacetate (17 mL, 146.0 mmol) in DCM (250 mL) was slowly added aluminum trichloride (25.5 g, 192.0 mmol) at 0° C.
After the addition was completed, the reaction was allowed to warm to room temperature and stir for another 12 h.
The reaction was diluted with EtOAc (500 mL) and washed with water (300 mL) and brine (300 mL).
The organic layer was separated, dried over Na2SO4, filtered and concentrated.
The residue was purified by silica gel column chromatography (PE:EtOAc=10:1 to 5:1) to afford the title compound (14 g, 67percent) as a light oil. MS (ES+) C10H9ClO3 requires: 212, 214. found: 213, 215 [M+H]+.
Reference: [1] Journal of Organic Chemistry, 1996, vol. 61, # 18, p. 6407 - 6415
[2] Patent: US2017/22206, 2017, A1, . Location in patent: Paragraph 0174; 0175; 0176
[3] Journal of Organic Chemistry, 2008, vol. 73, # 10, p. 3842 - 3847
[4] Organic Letters, 2011, vol. 13, # 24, p. 6520 - 6523
[5] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2013, vol. 52, # 6, p. 818 - 823
[6] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 8, p. 1958 - 1962
[7] Tetrahedron, 2017, vol. 73, # 39, p. 5813 - 5819
  • 38
  • [ 348-52-7 ]
  • [ 4755-77-5 ]
  • [ 1813-93-0 ]
Reference: [1] Angewandte Chemie - International Edition, 2018, vol. 57, # 24, p. 7176 - 7180[2] Angew. Chem., 2018, vol. 130, # 24, p. 7294 - 7298,5
  • 39
  • [ 4755-77-5 ]
  • [ 108-90-7 ]
  • [ 7099-88-9 ]
Reference: [1] Bulletin de la Societe Chimique de France, 1959, p. 850,852
[2] Collection of Czechoslovak Chemical Communications, 1964, vol. 29, p. 97 - 120
  • 40
  • [ 108-86-1 ]
  • [ 4755-77-5 ]
  • [ 20201-26-7 ]
YieldReaction ConditionsOperation in experiment
60% With aluminum (III) chloride In dichloromethane at 0 - 20℃; for 18 h; [0158] To a stirred mixture ofbromobenzene (0.7 mL, 6.5mmol) and ethyl 2-chloro-2-oxoacetate (0.7 mL, 6.5 mmol)in dichloromethane (12 mL) was added aluminum trichloride(L7 g, 12.5 mmol) at oo C, The reaction was warmed toRTslowly and stirred at RT for 18 h. After poured into cone.hydrochloric acid at oo C, the mixture was extracted withdichloromethane (3x100 mL). The combined organic layerswere washed with brine (100 mL), dried over anhydroussodium sulfate and filtered and concentrated under reducedpressure. The resultant oily matter was purified by silica gelcolunm chromatography (ethyl acetate:petroleum ether=:20) to afford the title compound (1 .0 g, 60percent) as a yellow oiLMS (ES+) C10H9Br03 requires: 256. found: 257, 259[M+Ht.
Reference: [1] Journal of Organic Chemistry, 1996, vol. 61, # 18, p. 6407 - 6415
[2] Tetrahedron Letters, 2006, vol. 47, # 16, p. 2675 - 2678
[3] Chemical Science, 2018, vol. 9, # 48, p. 8930 - 8936
[4] Patent: US2016/31892, 2016, A1, . Location in patent: Paragraph 0156-0158
[5] Journal of Organic Chemistry, 2008, vol. 73, # 10, p. 3842 - 3847
[6] Patent: WO2011/4276, 2011, A1, . Location in patent: Page/Page column 136
[7] Patent: WO2015/42397, 2015, A1, . Location in patent: Paragraph 000697
[8] Tetrahedron, 2017, vol. 73, # 39, p. 5813 - 5819
[9] Patent: WO2006/113471, 2006, A2, . Location in patent: Page/Page column 53
  • 41
  • [ 589-87-7 ]
  • [ 4755-77-5 ]
  • [ 20201-26-7 ]
Reference: [1] Angewandte Chemie - International Edition, 2018, vol. 57, # 24, p. 7176 - 7180[2] Angew. Chem., 2018, vol. 130, # 24, p. 7294 - 7298,5
  • 42
  • [ 4755-77-5 ]
  • [ 109-92-2 ]
  • [ 76240-19-2 ]
YieldReaction ConditionsOperation in experiment
87.8% at 33 - 36℃; for 2 h; A three-necked round bottom flask was charged with 1,4-dioxane (6.8 mL), triethylamine (2.96 g, 0.0293 mol) and ethyl vinyl ether (7.37 g, 0.102 mol). The resulting solution was warmed to 30C under nitrogen. Ethyl chlorooxoacetate (2.73 g, 0.02 mol) was added via syringe over 5 min., and the reaction was allowed to stir at 33-36C for 2h. The reaction mixture was cooled to room temperature, and filtered to remove solid. To the crude oil obtained by concentration was added water (15 mL). The resultant mixture was extracted with ethyl acetate (15 mL). The organic layer was dried over sodium sulfate and concentrated to the title compound as a light brown oil (3.02 g, 87.8percent). 1H NMR (CDCl3): δ 7.86 (d, 1H, J=12.6Hz), 6.17 (d, 1H, /=12.6Hz), 4.30 (q, 2H, .7=1.7 Hz), 4.05 (q, 2H, J=7.1Hz), 1.36(m,6H).
Reference: [1] Patent: WO2004/111011, 2004, A2, . Location in patent: Page 27; 2
[2] European Journal of Organic Chemistry, 2013, # 19, p. 4131 - 4145
[3] European Journal of Medicinal Chemistry, 2018, vol. 155, p. 96 - 116
[4] Patent: WO2009/123714, 2009, A2, . Location in patent: Page/Page column 52
[5] Patent: WO2012/73138, 2012, A1, . Location in patent: Page/Page column 68
  • 43
  • [ 5468-37-1 ]
  • [ 4755-77-5 ]
  • [ 84978-66-5 ]
YieldReaction ConditionsOperation in experiment
66% With triethylamine In dichloromethane at 0 - 20℃; for 16 h; Triethylamine (36 mL, 262.1 mmol) was added to a solution of 2-aminoacetophenone hydrochloride (15.0 g, 87.39 mmol) in dry CH2Cl2 (300 mL), followed by ethyl chlorooxoacetate (10 mL, 87.39 mmol) at 0 °C.
The reaction mixture was allowed to warm up to room temperature and stirred for 16 h.
The mixture was then diluted with water and extracted with EtOAc.
The combined extracts were washed with H2O and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure.
The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 20-30percent EtOAc in petroleum ether) to afford ethyl 2-oxo-2-((2-oxo-2-phenylethyl)amino)acetate (13.5 g, yield 66percent).
1H NMR (400 MHz, CDCl3) δ 8.09 (br s, 1 H), 8.02 - 8.00 (m, 2H), 7.68 - 7.64 (m, 1 H), 7.55 - 7.51 (m, 2H), 4.85 - 4.84 (d, J = 4.9 Hz, 2H), 4.44 - 4.39 (q, J = 7.0 Hz, 2H), 1.44-1.41 (t, J = 7.2 Hz, 3H). MS (ESI) m/z: Calculated for C12H13NO4: 235.08; found: 236.2 (M+H)+.
66% With triethylamine In dichloromethane at 0 - 20℃; for 16 h; Triethylamine (36 mL, 262.1 mmol) was added to a solution of 2-aminoacetophenone hydrochloride (15.0 g, 87.39 mmol) in dry CH2C12 (300 mL) the solution was cooled down to 0°C. Ethyl chlorooxoacetate (10 mL, 87.39 mmol) was added. The reaction mixture was warmed up to room temperature and stirred for 16 hours. The mixture was diluted with water and extracted with EtOAc (3 x 200 mL). The combined organic phase was washed with H20, brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 200-300 mesh, PE/EA = 5:1) to afford ethyl 2-oxo-2-((2-oxo-2-phenylethyl)amino)acetate (13.5 g, yield 66percent). ‘H NMR (400 MI-Tz, CDC13): δ 8.09 (br s, 1 H), 8.02 - 8.0 (m, 2H), 7.68-7.64 (m, 1 H), 7.55-7.51 (m, 2H), 4.85-4.84 (d, J= 4.9 Hz, 2H), 4.44-4.39 (q, J= 7.0 Hz, 2H), 1.44-1.41 (t, J 7.2 Hz,3H). MS (ESI) m/z = 236 [M+Hf’.
0.58 g
Stage #1: With triethylamine In dichloromethane at 0℃; for 0.25 h;
Stage #2: at 0 - 20℃; for 36 h;
To a solution of 2-amino-1-phenylethanone hydrochloride (0.50 g, 2.91 mmol) in DCM (5ml) was added TEA (0.58 g, 5.83 mmol) at 0°C. The reaction mixture was stirred at 0°C for 15 mm.Ethyl chlorooxoacetate (0.44 g, 3.21 mmol) was added slowly to the reaction mixture at 0°C. The reaction mixture was stirred at rt for 36 h. The resulting reaction mixture was poured into saturated NaHCO3 solution (10 ml) and extracted with DCM (2 x 10 ml). The combined organic phase was collected and washed with brine (10 ml), dried over Na2SO4, filtered and concentrated under reducedpressure yielding ethyl 2-oxo-2-((2-oxo-2-phenylethyl)amino)acetate (0.58 g, 2.46 mmol). LCMS:Method C, 1.79 mi MS: ES+ 236.33.
Reference: [1] Patent: EP2533783, 2015, B1, . Location in patent: Paragraph 0609-0610
[2] Patent: WO2018/58148, 2018, A1, . Location in patent: Paragraph 0256
[3] Chemische Berichte, 1914, vol. 47, p. 3166
[4] Patent: WO2005/61510, 2005, A1, . Location in patent: Page/Page column 16-17
[5] Patent: WO2017/103614, 2017, A1, . Location in patent: Page/Page column 62
  • 44
  • [ 4755-77-5 ]
  • [ 613-89-8 ]
  • [ 84978-66-5 ]
YieldReaction ConditionsOperation in experiment
73% With triethylamine In dichloromethane at 20℃; for 72 h; To a solution of 1-1 (5.0 g, 29.1 mmol) and triethylamine (8.5 mL, 61.1 mmol) in Dichloromethane was added drop-wise ethyl oxalyl monochloride (4.4 g, 32.0 mmol). The reaction mixture was stirred at room temperature for 72 hours. The mixture was quenched with ice water (200 mL), extracted with dichloromethane, washed with brine, dried with anhydrous Na2SO4, filtered and concentrated to give the crude product. The crude product was purified by silica gel chromatography eluted to give product 1-2 (5.0 g, 73.0percent) MS m/z [ESI]: 236.1 [M+1].
Reference: [1] Patent: US2018/271846, 2018, A1, . Location in patent: Paragraph 0132-0134
[2] ChemMedChem, 2012, vol. 7, # 6, p. 1020 - 1030
[3] European Journal of Medicinal Chemistry, 2015, vol. 101, p. 334 - 347
  • 45
  • [ 3731-51-9 ]
  • [ 4755-77-5 ]
  • [ 81803-60-3 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 8, p. 2354 - 2358
  • 46
  • [ 3290-99-1 ]
  • [ 4755-77-5 ]
  • [ 99367-44-9 ]
Reference: [1] Organic Process Research and Development, 2016, vol. 20, # 3, p. 675 - 682
  • 47
  • [ 59020-10-9 ]
  • [ 4755-77-5 ]
  • [ 73672-37-4 ]
Reference: [1] Journal of Chemical Research, Miniprint, 1995, # 10, p. 2422 - 2434
  • 48
  • [ 79099-07-3 ]
  • [ 4755-77-5 ]
  • [ 98977-34-5 ]
Reference: [1] ACS Medicinal Chemistry Letters, 2013, vol. 4, # 1, p. 63 - 68
  • 49
  • [ 625-99-0 ]
  • [ 4755-77-5 ]
  • [ 62123-73-3 ]
Reference: [1] Angewandte Chemie - International Edition, 2018, vol. 57, # 24, p. 7176 - 7180[2] Angew. Chem., 2018, vol. 130, # 24, p. 7294 - 7298,5
  • 50
  • [ 4076-36-2 ]
  • [ 4755-77-5 ]
  • [ 888504-28-7 ]
YieldReaction ConditionsOperation in experiment
90.8%
Stage #1: With triethylamine In toluene at 0 - 65℃; for 3 h;
Stage #2: With potassium hydroxide; water In ethanol at 10 - 20℃; for 1.16667 h;
Ethyl oxalylchloride (3.78 kg) was slowly added to a mixture of 5-methyltetrazole (2.50 kg), triethylamine (2.86 kg) in toluene (32 L) at O0C at such a rate that the temperature stays below 5°C. The resulting slurry was stirred for 1 hour at 0-50C then heated to 60-650C over 1 hour (N2 gas evolution). The slurry was aged at 60-650C for 1 hour and then cooled down to 20-250C. The triethylamine/HCl salt was filtered off. The solid was washed with 27 L of toluene. The combined filtrates were washed with 5 L of 10percent brine, then solvent switched to ethanol (reduced to 81, then 17 L of EtOH was added, then concentrated down to 8 L, then 33 liters of EtOH were added to adjust final volume of 41 L). The ethanol solution was cooled to 100C and KOH aq. (8.0 L) was added over 30 minutes, and the resulting thick slurry was then stirred for 40 minutes at room temperature while the oxadiazole K salt crystallized out. The solid was filtered off, washed with 1 1 L of EtOH and finally with 15 L of MTBE. The solid was dried overnight under vacuum at 200C with a nitrogen stream to yield 4.48 kg (90.8 percent) of the K-salt i.
90.8%
Stage #1: With triethylamine In toluene at 0 - 5℃; for 1 h;
Stage #2: at 50 - 65℃; for 1.66667 - 1.83333 h;
Stage #3: With potassium hydroxide In ethanol; water at 10 - 20℃; for 1.16667 h;
Material Eq. Mole Mass Volume Density 5-methyltetrazole 1.0 28.54 2.5 kg (2.4 kg) (96 wt. percent) ethyloxalyl 1.03 29.4 4.014 kg 3.29 L 1.22 chloride triethylamine 1.05 29.97 3.033 kg 4.21 L 0.72 toluene 74 L EtOH 61 L (punctilious) MTBE 15 L KOH aq. 8 L *20 wt. percent) 10percent brine 5 L Ethyl oxalylchloride (4.01 kg) was slowly added to a mixture of 5-methyltetrazole (2.50 kg), triethylamine (3.03 kg) in toluene (32 L) at 0° C. at such a rate that the temperature stays below 5° C. The resulting slurry was stirred for 1 hour at 0-5° C. then the triethylamine/HCl salt was filtered off. The solid was washed with 27 L of cold toluene (5° C.). The combined filtrates were kept at 0° C. and were slowly added to a hot solution of toluene (50° C., 15 L) over 40-50 minutes (N2 gas evolution), then the solution was aged at 60-65° C. for 1 hour. After cooling at 20° C., the toluene solution was washed with 5 L of 10percent brine, then solvent switched to ethanol (reduced to 8 L, then 17 L of EtOH was added, then concentrated down to 8 L, then 33 liters of EtOH were added to adjust final volume of 41 L). The ethanol solution was cooled to 10° C. and KOH aq. (8.0 L) was added over 30 minutes, and the resulting thick slurry was then stirred for 40 minutes at room temperature while the oxadiazole K salt crystallized out. The solid was filtered off, washed with 11 L of EtOH and finally with 15 L of MTBE. The solid was dried overnight under vacuum at 20° C. with a nitrogen stream to yield 4.48 kg (90.8percent) of the K-salt i.
Reference: [1] Patent: WO2007/87188, 2007, A2, . Location in patent: Page/Page column 36-37
[2] Patent: US2006/122205, 2006, A1, . Location in patent: Page/Page column 24-25
  • 51
  • [ 1068-57-1 ]
  • [ 4755-77-5 ]
  • [ 869108-50-9 ]
Reference: [1] Patent: EP1748048, 2007, A1, . Location in patent: Page/Page column 39
Recommend Products
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 4755-77-5 ]

Acyl Chlorides

Chemical Structure| 5781-53-3

[ 5781-53-3 ]

Methyl 2-chloro-2-oxoacetate

Similarity: 0.93

Chemical Structure| 13831-31-7

[ 13831-31-7 ]

Acetoxyacetylchloride

Similarity: 0.86

Chemical Structure| 39061-59-1

[ 39061-59-1 ]

tert-Butyl 2-chloro-2-oxoacetate

Similarity: 0.85

Esters

Chemical Structure| 5781-53-3

[ 5781-53-3 ]

Methyl 2-chloro-2-oxoacetate

Similarity: 0.93

Chemical Structure| 13831-31-7

[ 13831-31-7 ]

Acetoxyacetylchloride

Similarity: 0.86

Chemical Structure| 39061-59-1

[ 39061-59-1 ]

tert-Butyl 2-chloro-2-oxoacetate

Similarity: 0.85