Home Cart 0 Sign in  
X

[ CAS No. 667-27-6 ] {[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 667-27-6
Chemical Structure| 667-27-6
Chemical Structure| 667-27-6
Structure of 667-27-6 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 667-27-6 ]

Related Doc. of [ 667-27-6 ]

Alternatived Products of [ 667-27-6 ]

Product Details of [ 667-27-6 ]

CAS No. :667-27-6 MDL No. :MFCD00042069
Formula : C4H5BrF2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :IRSJDVYTJUCXRV-UHFFFAOYSA-N
M.W :202.98 Pubchem ID :69585
Synonyms :

Safety of [ 667-27-6 ]

Signal Word:Danger Class:3,8
Precautionary Statements:P210-P235-P240-P241-P242-P243-P260-P264-P280-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P321-P363-P370+P378-P403+P235-P405-P501 UN#:2924
Hazard Statements:H225-H314 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 667-27-6 ]

* 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 [ 667-27-6 ]
  • Downstream synthetic route of [ 667-27-6 ]

[ 667-27-6 ] Synthesis Path-Upstream   1~18

  • 1
  • [ 667-27-6 ]
  • [ 354-08-5 ]
Reference: [1] Israel Journal of Chemistry, 1964, vol. 2, p. 355 - 361
  • 2
  • [ 667-27-6 ]
  • [ 140-88-5 ]
  • [ 428-97-7 ]
YieldReaction ConditionsOperation in experiment
97.4% With N,N,N,N,-tetramethylethylenediamine; copper; acetic acid In tetrahydrofuran at 50℃; for 0.5 h; Copper powder (700 mg of) and tetrahydrofuran (5.8 mL of) added to the reaction vessel, and stirred at 50 , thereto was added ethyl acrylate (0.50 g of) and ethyl bromodifluoroacetate (2.53 g), followed by successively thereto solution of TMEDA (0.29g) and acetic acid (0.27g). The reaction for 0.5 hours and then ends. To the resulting mixture was added 10percent aqueous ammonium chloride solution, and the resulting mixture was filtered through a celite pad to remove the copper residue, and extracted with methyl t-butyl ether to obtain diethyl 2,2-difluoroglutarate ( 1.09g, yield 97.4percent).Furthermore, in addition to water (0.10g) acetic acid Alternatively, the same method as described above carried out to obtain diethyl 2,2-difluoro-glutarate (1.08 g of, yield 96.4percent).
55.0 g With N,N,N,N,-tetramethylethylenediamine; copper In tetrahydrofuran at 50℃; for 3 h; Preparation 1
Synthesis of diethyl 2,2-difluoropentanedioate
To a solution of ethyl bromodifluoroacetate (33.2 g) in tetrahydrofuran (94.0 g) was added ethyl acrylate (8.2 g) and copper powder (10.9 g).
After heating to 50° C., TMEDA (9.5 g) was added dropwise and the reaction mixture was then stirred for 3 hours at the same temperature.
Upon disappearance of ethyl acrylate as the starting material, to the reaction solution was added methyl t-butyl ether (MTBE, 73.7 g) followed by addition of 10percent aqueous ammonium chloride solution (49.8 g) dropwise, and the mixture was then stirred for 30 minutes.
The remaining copper residue was removed by filtration through a celite, and methyl t-butyl ether (MTBE, 66.3 g) was added to separate the layers.
The separated organic layer was washed successively with 10percent aqueous NH4Cl solution (66.3 g) and 3 N aqueous hydrochloric acid solution (99.6 g) in order and then distilled under reduced pressure to obtain 55.0 g of the desired title compound.
1H NMR (400 MHz, CDCl3) δ 1.26 (t, J=7.2 Hz, 3H), 1.37 (t, J=7.2 Hz, 3H), 2.37-2.49 (m, 2H), 2.55 (t, J=7.2 Hz, 2H), 4.16 (q, J=7.2 Hz, 2H), 4.29 (q, J=7.2 Hz, 2H).
Reference: [1] Patent: CN104159884, 2016, B, . Location in patent: Paragraph 0060; 0061; 0062; 0063; 0064
[2] Synthesis, 2012, vol. 44, # 20, p. 3165 - 3170,6
[3] Patent: WO2009/82134, 2009, A2, . Location in patent: Page/Page column 41-42
[4] Patent: WO2012/30106, 2012, A2, . Location in patent: Page/Page column 11
[5] Patent: US2013/165659, 2013, A1, . Location in patent: Paragraph 0098; 0099; 0100
  • 3
  • [ 667-27-6 ]
  • [ 140-88-5 ]
  • [ 428-97-7 ]
  • [ 1412175-17-7 ]
Reference: [1] Synthesis, 2012, vol. 44, # 20, p. 3165 - 3170,6
  • 4
  • [ 667-27-6 ]
  • [ 140-88-5 ]
  • [ 454-31-9 ]
  • [ 428-97-7 ]
Reference: [1] Synthesis, 2012, vol. 44, # 20, p. 3165 - 3170,6
  • 5
  • [ 637-87-6 ]
  • [ 667-27-6 ]
  • [ 130754-19-7 ]
YieldReaction ConditionsOperation in experiment
46% With copper In dimethyl sulfoxide at 80℃; for 20 h; To a stirred solutIon of I-chioro-4-iodobenzene (15.0 g, 63 mmo) and ethyl 2-bromo- 2,2—ditluoroacetate (12.8g. 63 mmo1 in DMS() (300 mL) was added Cu powder (8.0g. 126 nimol). i’he mixture was heated to 80 °C, and stirred for 20 hrs. The mixture was cooled to it, and poured into an aqueous solution of K2HPO4.3N20 (1 1.0 g) in water (1.5 L) under sdrring After stirring for 30 mm at rt, the mixture was filtered through a pad of celite. The filter cake was extracted with ether.The conibned organic phases were washed with waler and brine, dried over Na2SO4 and concentrated, The concentrate was purified column chromatography over silica gel (eluent: hexane) to afford the title compound as a colorless oil (6.8 g, 46percent). K NMR. (400 MHz, CDCI3) 67.55 jd, ,J 8.4 Hz, 211), 7.44 (d, .1 8.4 Hz, 2K), 4.30 (q, J 7.1 Hz,2H), 1.31 (t,J7.l Hz,3H).
Reference: [1] Patent: WO2016/44323, 2016, A1, . Location in patent: Paragraph 0368
[2] Chemical Communications, 2016, vol. 52, # 8, p. 1598 - 1601
[3] European Journal of Organic Chemistry, 2016, vol. 2016, # 33, p. 5529 - 5538
[4] Patent: WO2006/113471, 2006, A2, . Location in patent: Page/Page column 26; 48
  • 6
  • [ 667-27-6 ]
  • [ 130754-19-7 ]
YieldReaction ConditionsOperation in experiment
112 g
Stage #1: With trans-N,N,N′,N'-tetramethylcyclohexane-1,2-diamine; cobalt(II) chloride In tetrahydrofuran at 20℃; for 0.0833333 h; Inert atmosphere
Stage #2: at 0 - 20℃; for 19 h; Inert atmosphere
General procedure: General procedure for Co-catalyzed cross-coupling reaction of ethyl bromodifluoroacetate (4) with arylzinc reagent 3-TMEDA complex. To a stirred suspension of ZnCl2-TMEDA (505 mg, 2.0 mmol) in anhydrous THF (0.50 ml) was added dropwise a solution of ArMgX in anhydrous THF or Et2O (2.0 equiv) at 0 °C under Ar and the resulting mixture was stirred at room temperature for 30 min to prepare arylzinc reagent 3-TMEDA complex. To a solution of anhydrous cobalt (II) chloride (6.5 mg, 0.050 mmol) in anhydrous THF (3.0 ml) was added trans-1,2-bis(dimethylamino)cyclohexane (6) (10.2 mg, 0.060 mmol) and ethyl bromodifluoroacetate (4) (0.13 ml, 1.0 mmol) sequentially at room temperature under Ar and the resulting mixturewas stirred at room temperature for 5 min. To this resulting mixture was added dropwise the above prepared mixture of arylzinc reagent 3-TMEDA complex in THF at 0 C and the resulting mixture was stirred at room temperature for an indicated reaction time. The reaction mixture was quenched with 13percent aqueous NH4Cl solution (2.0 ml) and extracted with ether (4.0 ml 3). The extract was washed with water (4.0 ml) and brine (4.0 ml), then dried over MgSO4. Concentration of the solvent in vacuo afforded a residue, which was purified by silica gel column chromatography (hexane/ethyl acetate) to give ethyl 2-aryl-2,2-difluroacetate 5.#10;
Reference: [1] Tetrahedron, 2013, vol. 69, # 19, p. 3913 - 3918
  • 7
  • [ 667-27-6 ]
  • [ 24850-33-7 ]
  • [ 110482-96-7 ]
Reference: [1] Journal of Fluorine Chemistry, 2004, vol. 125, # 4, p. 509 - 515
  • 8
  • [ 667-27-6 ]
  • [ 87189-16-0 ]
YieldReaction ConditionsOperation in experiment
95% With potassium hydroxide In methanol at 20℃; Into the solution of KOH (56 g, 1 mol) in methanol (500 mL) was slowly added BrCF2CO2Et (203 g, 1 mol) at room temperature. The resulting mixture was stirred at the same temperature until BrCF2CO2Et was completely consumed. The solvent was removed by concentration to give BrCF2CO2K as a solid (202 g, 95percent).
Reference: [1] Journal of Fluorine Chemistry, 2014, vol. 163, p. 38 - 41
[2] Chemical Communications, 2013, vol. 49, # 68, p. 7513 - 7515
[3] Angewandte Chemie - International Edition, 2018, vol. 57, # 46, p. 15081 - 15085[4] Angew. Chem., 2018, vol. 130, # 46, p. 15301 - 15305,5
[5] Organic Letters, 2017, vol. 19, # 15, p. 4150 - 4153
[6] Organic Letters, 2016, vol. 18, # 1, p. 44 - 47
  • 9
  • [ 624-28-2 ]
  • [ 667-27-6 ]
  • [ 77199-09-8 ]
YieldReaction ConditionsOperation in experiment
81%
Stage #1: With copper In dimethyl sulfoxide at 20℃; for 1 h;
Stage #2: at 20℃; for 15 h;
SYNTHESIS OF INTERMEDIATE KETONE B2-(5-Bromopyridin-2-yl)- 1-(2,4-difluorophenyl)-2,2-difluoroethanone (B) To a suspension of copper powder (2.68 grams (g), 42.2 millimoles (mmol)) in dimethyl sulfoxide(DMSO; 35 milliliters (mL)) was added ethyl 2-bromo-2,2-difluoroacetate (2.70 mL, 21.10mmol), and the mixture was stirred for 1 hour (h) at room temperature (RT). 2,5-Dibromopyridine(2.50 g, 10.55 mmol) was then added, and stirring was continued for 15 h at RT. The reactionmixture was quenched with aqueous (aq) ammonium chloride (NH4C1) and extracted withdichloromethane (CH2C12 3 x 25 mL). The combined organic layers were washed with water (H20), washed with brine, dried over anhydrous sodium sulfate (Na2SO4), and concentrated under reduced pressure to afford the crude product mixture. Purification by column chromatography (eluting with ethyl acetate (EtOAc)/hexane) afforded the ethyl ester intermediate (2.40 g, 8.57mmol, 81percent) as a pale yellow oil. ‘H NMR (500 MHz, CDC13): ö 8.71 (s, 1H), 8.00 (d, J 9.0 Hz,1H), 7.64 (d, J= 9.0 Hz, 1H), 4.42-4.35 (m, 2H), 1.39-1.3 1 (m, 3H).
Reference: [1] Patent: WO2014/43376, 2014, A1, . Location in patent: Page/Page column 46; 47
  • 10
  • [ 667-27-6 ]
  • [ 99-93-4 ]
  • [ 83882-67-1 ]
Reference: [1] Advanced Synthesis and Catalysis, 2018, vol. 360, # 21, p. 4161 - 4167
  • 11
  • [ 667-27-6 ]
  • [ 139-85-5 ]
  • [ 151103-08-1 ]
Reference: [1] Organic and Biomolecular Chemistry, 2018, vol. 16, # 38, p. 6900 - 6908
  • 12
  • [ 667-27-6 ]
  • [ 57684-32-9 ]
  • [ 541547-36-8 ]
YieldReaction ConditionsOperation in experiment
95%
Stage #1: With chloro-trimethyl-silane; zinc In tetrahydrofuran for 0.25 h;
Stage #2: for 2 h;
[00331j Step 1: To a stirred suspension of Zn dust (4.98 g, 76 mmol) in THF (100 mL)was added TMS-Cl (9.73 mL, 76 mmol) followed by the addition of ethyl 2-bromo-2,2-difluoroacetate (3.40 g, 16.75 mmol). The mixture was stirred for 15 minutes, then a solution of N-(( 1 H-benzo [d] [1,2,3 ]triazol- 1 -yl)methyl)-N-benzyl- 1 -phenylmethanamine (5 g, 15.22 mmol) in THF (50 mL) was added slowly. The reaction mixture was stirred for 2 hours. The reaction was quenched slowly by the addition of 10percent sodium-bi15 carbonate solution and extracted with ethyl acetate (3x200 mL). The combined organiclayers were washed with water, dried over sodium sulphate and concentrated. The crude material was purified via column chromatography to afford ethyl 3-(dibenzylamino)-2,2- difluoropropanoate (5 g, 95percent yield) as a pale yellow oil. LCMS 334.2 (M+H).
95%
Stage #1: With chloro-trimethyl-silane; zinc In tetrahydrofuran for 0.25 h;
Stage #2: for 2 h;
To a stirred suspension of Zn dust (4.98 g, 76 mmol) in THF (100 mL) was added TMS-Cl (9.73 mL, 76 mmol) followed by the addition of ethyl 2-bromo-2,2-difluoroacetate (3.40 g, 16.8 mmol). The mixture was stirred for 15 minutes, then a solution of N-((1 H-benzo [dl [1,2,3 jtriazol- 1 -yl)methyl)-N-benzyl-1- phenylmethanamine (5 g, 15.22 mmol) in THF (50 mL) was added slowly. The reaction mixture was stirred for 2 hours. The reaction was quenched slowly by the addition of 10percent sodium-bicarbonate solution. The reaction mixture was extracted with ethyl acetate(3x200 mL). The combined organic layers were washed with water, dried over sodium sulfate and concentrated. The crude material was purified via column chromatography to afford ethyl 3-(dibenzylamino)-2,2- difluoropropanoate (5 g, 95percent yield) as a pale yellowoil. LCMS 334.2 (M+H).
94%
Stage #1: With chloro-trimethyl-silane; zinc In tetrahydrofuran at 20℃; for 0.333333 h;
Stage #2: at 20℃; for 1 h;
Stage #3: With sodium hydrogencarbonate In tetrahydrofuran; water for 0.166667 h;
To a suspension of zinc dust (238 mg, 3.66 mmol) in dry THF (3 mL), under Ar, was added TMSCl (234 μL, 1.83 mmol) and the reaction mixture stirred at ambient temperature for 10 min. Ethyl bromodifluoroaetate (260 μL, 2.0 mmol) was added dropwise and the resulting slurry stirred for 10 min. N-((1H-benzo[d] [1,2,3]triazol-1-yl)methyl)-N-benzyl-1-phenylmethanaime (600 mg, 1.83 mmol) in dry THF (3 mL) was then added and the reaction mixture stirred at room temperature for 1 h. To the reaction mixture was added 10 ml 5percent NaHCO3 (aq). The resulting mixture was stirred for 10 min, and filtered through a celite pad. The filtrate was extracted with EtOAc and the celite pad was rinsed with EtOAc. The combined EtOAc portions was dried over MgSO4, filtered, concentrated and purified by ISCO flash chromatography, using EtOAc and hexane as eluting solvent, to yield ethyl 3-(dibenzylamino)-2,2-difluoropropanoate as a colorless oil (577 mg, 94percent yield). LCMS: RT=4.09 min [M+H] 334.28 (LCMS Method 1).
94.6% With chloro-trimethyl-silane; zinc In tetrahydrofuran at 20℃; for 2 h; Step 2: To a stirred suspension of zinc dust (0.795 g, 12.18 mmol) in THF (20 mL) was added TMSCl (0.662 g, 6.09 mmol), followed by ethyl 2-bromo-2,2-difluoroacetate (1.360 g, 6.70 mmol). The reaction mixture was stirred for 15 min and a solution of N-((1H-benzo[d][1,2,3]triazol-1-yl)methyl)-N-benzyl-1-phenylmethanamine (2 g, 6.09 mmol) in THF (20 mL) was added dropwise. The reaction mixture was allowed to stir for 2 h at room temperature. The reaction mixture was diluted with aqueous NaHCO3 and EtOAC. The aqueous layer was extracted with EtOAc (twice). The organic extracts were combined, dried over Na2SO4 and concentrated. The crude material was purified by flash column chromatography using silica gel as stationary phase and EtOAc: pet ether (0-10percent) as eluent to get ethyl 3-(dibenzylamino)-2,2-difluoropropanoate (1.8 g, 94.6percent yield). LC/MS: 334.6 (M+H).
56%
Stage #1: With chloro-trimethyl-silane; zinc In tetrahydrofuran at 20℃; for 0.333333 h;
Stage #2: at 20℃; for 1 h;
Stage #3: With sodium hydrogencarbonate In tetrahydrofuran; water
To a suspension of zinec dust (238 mg, 3.66 mmol) in THF (3 ml) under Ar was added TMSCl (234 uL, 1.83 mmol). The reaction mixture was stirred at rt for10 min followed by addition of ethyl bromodifluoroacetate (260 uL, 2.0 mmol) dropwise. After 10 min, N-((lH-benzo[(][l,2,3]triazol-l-yl)methyl)-N-benzyl-l- phenylmethanaime (600 mg, 1.83 mmol) in TηF (3 ml) was added and the reaction mixture was stirred at room temperature for 1 h. The reaction mixture was quenched with 5percent νaηCψ3 in H2O (10 mL). The resulting solid was filtered and washed with EtOAc. The filtrate was extracted with EtOAc and the combined EtOAc layers were dried over MgSO4, filtered and concentrated under reduced pressure. The resulting residue was purified by ISCO flash chromatography by using EtOAc and hexane as eluting solvent to yield ethyl 3-(diben2ylamino)-2,2-difluoropropanoate as a colorless011 (577 mg, 56percent yield). LCMS: RT = 4.09 min [M+H] 334.28 (Phenomenex Luna <n="317"/>C18 column, 4.6 x 50 mm eluting with 10-90percent MeOHTH2O over 4 minutes containing 0.1percent TFA; 4 mL/min, monitoring at 220 nm).
50%
Stage #1: With chloro-trimethyl-silane; zinc In tetrahydrofuran at 20℃; for 1.33333 h;
Stage #2: at 0 - 20℃; for 18.5 h;
Ethyl 3-(dibenzylamino)-2,2-difluoropropanoate: To a suspension of zinc dust (2.7 g, 41.6 mmol) in dry THF (75 mL), stirred under argon atmosphere, was added chlorotrimethylsilane (2.63 mL, 20.8 mmol) followed, 10 min later, by ethyl dibromo- fluoroacetate (3.92 g, 20.8 mmol). After 10 min a slight exotherm was detected. The reaction was left to activate for 1 hour, whereupon it was cooled in an ice bath and a solution of N-(Dibenzylaminomethyl)benzotriazole (6.83 g, 20.8 mmol) in THF (50 mL) was added dropwise (over 30 minutes) and then the reaction mixture was allowed to warm to room temperature. After 18 h at r.t., NaHCO3 (sat., 50 mL) was added, let stir for 20 minutes, the reaction was filtered on Celite, and the filter pad was washed with EtOAc. The layers were separated and the aqueous phase was extracted with EtOAc (3χ50 mL). The organic layers were combined and washed with IN HCl (70 mL), brine (70 mL), then dried over MgSO4. After evaporation of the solvent, the residue was poured into rapidly stirring ether (100 mL); the solid formed was removed by filtration and discarded. The ether was evaporated from the filtrate to yield a dark yellow syrup. This crude residue was purified on silica gel column chromatographically (0-10percent EtOAc:Hexanes) to yield the desired product as a clear liquid (3.6 g, 50 percent yield). 1H NMR in CDCl3: (400 MHz) δ ppm 1.18 (t, J=7.07 Hz, 3 H) 3.14 (t, J=13.26 Hz, 2 H) 3.69 (s, 4 H) 4.14 (q, J=7.16 Hz, 2 H) 7.14 - 7.33 (m, 10 H). [M+H] calc'd for Ci9H2iF2NO2, 334; found 334.
5.6 g
Stage #1: With chloro-trimethyl-silane; zinc In tetrahydrofuran at 10 - 35℃; for 0.0833333 h; Inert atmosphere
Stage #2: at 10 - 35℃; for 1 h;
(B)
Ethyl 3-(dibenzylamino)-2,2-difluoropropanoate
To a mixture of a zinc powder (3.25 g) and THF (50 mL), chlorotrimethylsilane (3.02 mL) was added at room temperature, and the resulting mixture was stirred at the same temperature for 2 minutes.
Ethyl bromodifluoroacetate (3.68 mL) was added dropwise to the reaction mixture at room temperature, and the mixture was stirred under nitrogen atmosphere at the same temperature for 5 minutes.
A solution of N-((1H-benzo[d][1,2,3]triazol-1-yl)methyl)-N-benzyl-1-phenylmethanamine (7.85 g) in THF (60 mL) was added dropwise to the reaction mixture at room temperature, and the mixture was stirred at the same temperature for 1 hour.
Saturated aqueous sodium bicarbonate solution was added to the reaction mixture at room temperature, and the mixture was stirred for 5 minutes.
Then, the reaction mixture was filtered, and the filtrate was extracted with ethyl acetate.
The extract was washed with brine and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure.
The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane) to obtain the title compound (5.6 g).
MS: [M+H]+ 334.0.
5.6 g
Stage #1: With chloro-trimethyl-silane; zinc In tetrahydrofuran at 20℃; for 7 h; Inert atmosphere
Stage #2: at 20℃; for 1 h; Inert atmosphere
At room temperature,In zinc powder (3.25 g)And THF (50 mL)Was added chlorotrimethylsilane (3.02 mL)The resulting mixture was stirred at the same temperature for 2 hours.A solution of ethyl bromodifluoroacetate (3.68 mL) was added dropwise to the reaction mixture at room temperature,And the mixture was stirred at room temperature for 5 hours under a nitrogen atmosphere. At room temperature,Add dropwise(1H-benzo [d] [1,2,3] triazol-1-yl) methyl) -N-benzyl-1-phenylmethanamine (7.85 g)THF (60 mL) was added to the reaction mixture,And the mixture was stirred at the same temperature for 1 hour.Saturated aqueous sodium bicarbonate was added to the reaction mixture, and the mixture was stirred for 5 minutes.The reaction mixture was then filtered and the filtrate was extracted with ethyl acetate.The extract was washed with brine and dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure.The residue was purified by silica gel column chromatography (NH, ethyl acetate / hexane) to give the title compound (5.6 g).

Reference: [1] Patent: WO2014/74675, 2014, A1, . Location in patent: Paragraph 00331
[2] Patent: WO2016/210036, 2016, A1, . Location in patent: Page/Page column 170; 171
[3] Tetrahedron Letters, 2003, vol. 44, # 11, p. 2375 - 2377
[4] Patent: US2007/161685, 2007, A1, . Location in patent: Page/Page column 460-461
[5] Patent: US2015/191464, 2015, A1, . Location in patent: Paragraph 0521
[6] Patent: WO2007/62308, 2007, A2, . Location in patent: Page/Page column 314-315
[7] Patent: WO2009/42711, 2009, A1, . Location in patent: Page/Page column 235; 236
[8] Patent: US2017/44132, 2017, A1, . Location in patent: Paragraph 0564; 0973; 0974
[9] Patent: TW2017/14883, 2017, A, . Location in patent: Paragraph 0334; 0335
  • 13
  • [ 95-14-7 ]
  • [ 50-00-0 ]
  • [ 667-27-6 ]
  • [ 103-49-1 ]
  • [ 541547-36-8 ]
Reference: [1] ACS Chemical Neuroscience, 2017, vol. 8, # 1, p. 40 - 49
  • 14
  • [ 667-27-6 ]
  • [ 4983-28-2 ]
  • [ 1192813-64-1 ]
YieldReaction ConditionsOperation in experiment
38% With caesium carbonate In N,N-dimethyl-formamide at 80℃; To a solution of 2-chloro-5-hydroxypyrimidine (4.13 g) in DMF (40 mL) were added ethyl 2-bromo-2,2-difluoroacetate (12.83 g) and cesium carbonate (20.59 g), and the mixture was reacted at 80°C overnight. The reaction solution was cooled to room temperature, and then poured into water. The mixture was extracted with ethyl acetate thrice. The organic layer was dried over magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel (hexane:ethyl acetate = 80:20 to 60:40) to give the titled compound (2.16 g) as a colorless liquid (yield 38percent). MS(APCI)m/z; Not detected.
Reference: [1] Patent: EP2390254, 2011, A1, . Location in patent: Page/Page column 88
  • 15
  • [ 529-28-2 ]
  • [ 667-27-6 ]
  • [ 1150164-80-9 ]
YieldReaction ConditionsOperation in experiment
96% With copper In dimethyl sulfoxide at 60℃; for 12 h; Inert atmosphere General procedure: To a suspension of activated Cu powder (2.6 eq.) in DMSO (0.38 M) was added the appropriate aryl iodide (1.0 eq.) and ethyl bromodifluoroacetate (1.0 eq.) or ethyl bromofluoroacetate (1.0 eq.) under nitrogen atmosphere. The reaction mixture was stirred at 60°C for 12 h. The reaction mixture was filtered through a pad of Celite® and washed with Et2O. The mixture was washed with aq. NH4Cl (sat., 2x) and brine (2x), then dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography.
Reference: [1] Synlett, 2016, vol. 27, # 1, p. 25 - 28
[2] Organic Letters, 2013, vol. 15, # 11, p. 2648 - 2651
[3] European Journal of Organic Chemistry, 2016, vol. 2016, # 33, p. 5529 - 5538
[4] European Journal of Organic Chemistry, 2017, vol. 2017, # 40, p. 6052 - 6059
  • 16
  • [ 667-27-6 ]
  • [ 100-66-3 ]
  • [ 915133-57-2 ]
  • [ 1150164-80-9 ]
  • [ 112545-98-9 ]
Reference: [1] European Journal of Organic Chemistry, 2015, vol. 2015, # 8, p. 1719 - 1726
[2] Advanced Synthesis and Catalysis, 2014, vol. 356, # 13, p. 2741 - 2748
  • 17
  • [ 667-27-6 ]
  • [ 4068-76-2 ]
  • [ 1131587-78-4 ]
YieldReaction ConditionsOperation in experiment
50% With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 24 h; To a solution of methyl 5-bromo-2-hydroxybenzoate (409 mg, 1.77 mmol) in DMF (5 mL) was added potassium carbonate (367 mg, 2.67 mmol) and ethyl 2-bromo-2,2-difluoroacetate (280 μ^, 2.13 mmol). The resulting mixture was heated at 80 °C for 24 hrs. The resulting solution was cooled to RT, diluted with ether and washed sequentially with water, 10percent aq. HCl, water and brine. The organic extract was then dried over Na2S04, filtered and the filtrate concentrated in vacuo. Further purification by way of column chromatography (S1O2, gradient elution, Hex to 2:1 (v/v) Hex: EtOAc) afforded methyl 5-bromo-2- (difluoromethoxy)benzoate as a yellow oil (250 mg, 50percent yield).
Reference: [1] Patent: WO2013/134562, 2013, A1, . Location in patent: Paragraph 00294
  • 18
  • [ 357927-50-5 ]
  • [ 667-27-6 ]
  • [ 1416732-46-1 ]
  • [ 1189458-67-0 ]
Reference: [1] Organic Process Research and Development, 2018, vol. 22, # 10, p. 1441 - 1447
Same Skeleton Products
Historical Records