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Product Details of Ethyl 2-oxocyclohexanecarboxylate

CAS No. :1655-07-8
Formula : C9H14O3
M.W : 170.21
SMILES Code : C(OC(=O)C1C(=O)CCCC1)C
MDL No. :MFCD00001631
InChI Key :FGSGHBPKHFDJOP-UHFFFAOYSA-N
Pubchem ID :95543

Safety of Ethyl 2-oxocyclohexanecarboxylate

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of Ethyl 2-oxocyclohexanecarboxylate

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

  • Downstream synthetic route of [ 1655-07-8 ]

[ 1655-07-8 ] Synthesis Path-Downstream   1~19

  • 1
  • [ 37595-74-7 ]
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  • [ 122135-83-5 ]
YieldReaction ConditionsOperation in experiment
59% Step 1. Ethyl 2-(((trifluoromethyl)sulfonyl)oxy)cyclohex-l-enecarboxylate [0083] Sodium hydride (60 wt. % in oil, 228 mg, 5.70 mmol) was added to a 0 C solution of ethyl 2-oxocyclohexanecarboxylate (888 mg, 4.96 mmol) in THF (25 mL). After 40 min at 0 C, N-phenyl-bis(trifluoromethanesulfonimide) (2.14 g, 5.93 mmol) was added and the solution was allowed to warm to room temperature and stir overnight. The reaction mixture was quenched with saturated aqueous NaHC03 and extracted with CH2C12 (3x). The combined extracts were dried (MgS04), filtered and concentrated. The resulting crude residue was purified on a Teledyne-Isco Combiflash machine (120 g gold column, hexanes- 25% EtOAc/hexanes, gradient), to afford 879 mg (59%) of ethyl 2-(((trifluoromethyl)sulfonyl)oxy)cyclohex-l- enecarboxylate.
  • 2
  • [ 57508-48-2 ]
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  • [ 111655-66-4 ]
  • 3
  • [ 1655-07-8 ]
  • [ 119068-37-0 ]
  • [ 29569-79-7 ]
  • [ 61586-78-5 ]
  • [ 1655-06-7 ]
  • 7
  • [ 1004-38-2 ]
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  • [ 19191-79-8 ]
  • 8
  • [ 1004-38-2 ]
  • [ 1655-07-8 ]
  • 1,3-diamino-5,6,7,8-tetrahydro-2,9a,10-triazaanthracen-9-one [ No CAS ]
  • 2,4-diamino-5,6,7,8-tetrahydro-3,4a,10-triazaphenanthren-9-one [ No CAS ]
  • 9
  • [ 2406-90-8 ]
  • [ 1655-07-8 ]
  • 2,11-dichloro-7,8,9,10-tetrahydrothiazolo[5,4-a]acridine [ No CAS ]
  • 10
  • [ 358-23-6 ]
  • [ 1655-07-8 ]
  • [ 122135-83-5 ]
YieldReaction ConditionsOperation in experiment
90% In a 500mL three-necked flask, add 60% sodium hydrogen (3.5g, 1.5eq.),Add 200 mL of dichloromethane and replace with nitrogen three times.Under the condition of 0-5C, add ethyl 2-cyclohexanone carboxylate (10.0 g, 1.0eq.) dropwise, keep the temperature and stir for 10 min,Subsequently, the temperature continued to drop to -70C, and Tf2O (24.3g, 1.5eq.) was added dropwise to the reaction solution (to control the dropping rate),Incubate and stir for 15 minutes, then naturally heat to 25C and stir overnight;Afterwards, a saturated NaHCO3 solution was added to adjust the pH to 8-9, the organic phase was dried over anhydrous sodium sulfate, and concentrated to obtain Intermediate 1a (15.6g, 90.0% yield).
82% With N-ethyl-N,N-diisopropylamine; In dichloromethane; at -78 - 20℃; for 18h; Preparation 41; 2-Hydroxy-cyclohex-l-enecarboxylic acid ethyl ester; Et EPO <DP n="34"/>Combine 2-oxo-cyclohexanecarboxylic acid ethyl ester (10.0 g, 55.0 mmol), Hunig's base (23.0 mL, 132.0 mmol), dichloromethane (100.0 mL), and trifluoromethane sulphonic anhydride (11.1 mL, 66.0 mmol) at ""780C and then stir at room temperarture for 18 hours under a nitrogen atmosphere. Add water, then wash with sat sodium bicarbonate solution, citric acid, then brine, and dry over sodium sulfate. Concentrate under vacuum and flash chromatograph using 10% to 40% DCM/hexanes eluent to yield the titled compound (13.6 g, 82%). TLC Rf=0.25in 40% DCM/hexanes. 1H NMR (CDCl3): 4.26 (q, 2H, 7=7.0 Hz), 2.5 (m, 2H), 2.4 (m, 2H), 1.8 (m, 2H), 1.7 (m, 2H), 1.3 (t, 3H, 7=7 Hz).
76% With N-ethyl-N,N-diisopropylamine; In dichloromethane; at -78 - 20℃; for 16h; Ethyl 2-oxocyclohexanecarboxyla.te (170 mg, 1 .00 mmol) and DIEA (417 jjJL, 2,40 mmol) were dissolved in DCM (2 mL) and cooled to -78 C. To the stirring solution was added dropwise trifluoromethanesuiionic anhydride (202 μΤ, 1.20 mmol), then the resulting solution was allowed to warm to room temperature and stirred for 16 h. The solution was then diluted with DCM and washed with I M aqueous HCl and the solvent removed under reduced pressure. The crude residue was purified by flash column ehroniatograpliy using a gradient of hexanes : EtOAc (9 : 1 to 1 : 1) to give 29a (231 mg, 76%) as a clear oil. 1H~NMR (400 MHz, CDC13) δ 4.23 (q, J = 7.1 Hz, 2H), 2.51-2.40 (m, 2H), 2.40-2.31 (m, 2H), 1.81-1.70 (m, 2H), 1.70-1.57 (m, 2H), L28 (t, J= 7.1 Hz, 3H).
Example 1 (Intermediate); 2-Trifluoromethanesulfonyloxy-cyclohex-l-enecarboxylic acid ethyl (1); To a suspension of sodium hydride (1.35 g, 33.9 mmol) in diethyl ether (150 mL) was added dropwise a solution of ethyl 2-oxocyclohexanecarboxylate (5.00 g, 29.4 mmol) diethyl ether (30 mL). After stirring for 2 h at room temperature, trifluoromethanesulfonic anhydride (5.7 mL, 33.8 mmol) was added dropwise, and the reaction mixture was stirred for 16 h at room temperature. The reaction was quenched with saturated ammonium chloride (200 mL), and the product was extracted with ether (3x 100 mL). The combined ether extracts were dried over MgSO4, filtered, and concentrated to provide compound (1), which was used in the next step without further purification.
Example 8A ethyl 2-(trifluoromethylsulfonyloxy)cyclohex-1-enecarboxylate To a cooled (0 C.) stirring suspension of NaH (0.983 g 60% in mineral oil, washed with hexane three times) in ether (50 ml) was added ethyl 2-oxocyclohexanecarboxylate (3.2 g, 20.5 mmol). The mixture was stirred at 0 C. for 30 minutes before the addition of trifluoromethanesulfonic anhydride (4.2 mL, 25 mmol). The mixture was then stirred at room temperature overnight. The mixture was diluted with ether (200 mL) and washed with 5% HCl, water and brine. After drying over Na2SO4, evaporation of solvent gave crude product which was used without further purification.
General procedure: The NaH (60% oil dispersion, 23.4 mmol,0.94 g, 1.3 eq) was weighted into a 250-mL round-bottom flask, filled with 80 mL of CH2Cl2. Then the flask was placed into an ice bath and the β-ketoester (18 mmol, 5.0 g, 1.0 eq) was added dropwise over 10 min. This reaction mixture was stirred for 20 min at 0 C to complete deprotonation and then cooled down to -78 C. Trifluoromethanesulfonic anhydride (24.3 mmol, 6.90g, 1.35eq) was added dropwise and then warmed up slowly overnight for 12 h. It was quenched with brine, filtrated through Celite, extracted with CH2Cl2, concentrated in vacuo, and purified over silica gel to obtainedthe products.
To compound 1 (1 g, 5.88 mmol) in DCM (20 mL) was added NaH (0.29 g, 12 mmol) at 0 degrees. After replacing the nitrogen, stirring for 30 minutes, add trifluoromethanesulfonic anhydride Tf2O (2.0g, 7mmol) to the above reaction solution and slowly rise to room temperature and stir for 1-24 hours. After the reaction is complete, add 20ml of water to quench the reaction solution. Extract twice with methyl chloride (20 mL) and dry the organic phase. It was spin-dried to obtain 2.0 g of crude compound 2. The reaction is almost quantitative and can be used directly in the next step.

References: [1]Journal of the American Chemical Society,2003,vol. 125,p. 4804 - 4807.
[2]Journal of Organic Chemistry,2003,vol. 68,p. 969 - 973.
[3]Chemistry - A European Journal,2013,vol. 19,p. 3504 - 3511.
[4]Organic Letters,2018,vol. 20,p. 2993 - 2996.
[5]Patent: CN113135848,2021,A .Location in patent: Paragraph 0021-0024.
[6]Journal of Organic Chemistry,2016,vol. 81,p. 1391 - 1400.
[7]Patent: WO2006/88716,2006,A1 .Location in patent: Page/Page column 32-33.
[8]Patent: WO2013/96771,2013,A1 .Location in patent: Page/Page column 120; 121.
[9]Angewandte Chemie - International Edition,2019,vol. 58,p. 18476 - 18481.
    Angew. Chem.,2019,vol. 131,p. 18647 - 18652,6.
[10]Chemistry - A European Journal,2015,vol. 21,p. 6074 - 6078.
[11]Patent: WO2010/77530,2010,A1 .Location in patent: Page/Page column 41-42.
[12]Patent: US2010/184766,2010,A1 .Location in patent: Page/Page column 45.
[13]Angewandte Chemie - International Edition,2013,vol. 52,p. 11102 - 11105.
    Angewandte Chemie,2013,vol. 125,p. 11308 - 11311,4.
[14]Angewandte Chemie - International Edition,2014,vol. 53,p. 6180 - 6183.
    Angew. Chem.,2014,vol. 126,p. 6294 - 6297.
[15]Journal of the American Chemical Society,2018,vol. 140,p. 7587 - 7597.
[16]Organic Letters,2019,vol. 21,p. 1555 - 1558.
[17]Tetrahedron Letters,2019,vol. 60,p. 1148 - 1152.
[18]Advanced Synthesis and Catalysis,2020,vol. 362,p. 326 - 330.
[19]Chemical Communications,2020,vol. 56,p. 12817 - 12820.
[20]Angewandte Chemie - International Edition,2020,vol. 59,p. 20201 - 20207.
    Angew. Chem.,2020,vol. 132,p. 20376 - 20382,7.
[21]Patent: CN113636960,2021,A .Location in patent: Paragraph 0066-0069; 0074-0081; 0090-0092.
  • 11
  • [ 104-21-2 ]
  • [ 1655-07-8 ]
  • ethyl 1-[(4-methoxyphenyl)methyl]-2-cyclohexanonecarboxylate [ No CAS ]
  • 14
  • [ 29608-05-7 ]
  • [ 1655-07-8 ]
  • C21H31N3O4 [ No CAS ]
  • 15
  • [ 145100-51-2 ]
  • [ 1655-07-8 ]
  • [ 122135-83-5 ]
  • 16
  • [ 1655-07-8 ]
  • [ 122135-83-5 ]
YieldReaction ConditionsOperation in experiment
With trifluoromethylsulfonic anhydride; N-ethyl-N,N-diisopropylamine; In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; Step 1: ethyl 2-[(trifluoromethyl)sulfonyl]oxy}cyclohex-1-ene-1-carboxylate To a solution of ethyl cyclohexanone-2-carboxylate (5.02 g, 29.5 mmol) in DCM (100 mL) cooled to -78 C. was added DIPEA (25.4 mL, 146 mmol) and then triflic anhydride (5.98 mL, 35.4 mmol) dropwise. The mixture was then warmed to r.t. and stirred overnight. The reaction was then quenched with aqueous citric acid and extracted with additional water. The organic layer was dried over Na2SO4 and the solvent was removed in vacuo. The crude product was purified on silica (100% DCM) to give the title product as an oil.
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  • [ 2028-85-5 ]
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  • [ 59514-18-0 ]
  • 18
  • [ 38980-96-0 ]
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  • [ 1285661-67-7 ]
  • 19
  • [ 1655-07-8 ]
  • [ 4187-59-1 ]
  • [ 4187-60-4 ]
  • [ 1655-06-7 ]
  • [ 1655-06-7 ]
 

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