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Product Details of [ 151-10-0 ]

CAS No. :151-10-0 MDL No. :MFCD00008384
Formula : C8H10O2 Boiling Point : -
Linear Structure Formula :- InChI Key :DPZNOMCNRMUKPS-UHFFFAOYSA-N
M.W : 138.16 Pubchem ID :9025
Synonyms :
Resorcinol dimethyl ether

Calculated chemistry of [ 151-10-0 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 10
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.25
Num. rotatable bonds : 2
Num. H-bond acceptors : 2.0
Num. H-bond donors : 0.0
Molar Refractivity : 39.43
TPSA : 18.46 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.57 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.18
Log Po/w (XLOGP3) : 2.21
Log Po/w (WLOGP) : 1.7
Log Po/w (MLOGP) : 1.48
Log Po/w (SILICOS-IT) : 1.82
Consensus Log Po/w : 1.88

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.4
Solubility : 0.549 mg/ml ; 0.00397 mol/l
Class : Soluble
Log S (Ali) : -2.23
Solubility : 0.81 mg/ml ; 0.00586 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.62
Solubility : 0.329 mg/ml ; 0.00238 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.17

Safety of [ 151-10-0 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 151-10-0 ]

* 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 [ 151-10-0 ]
  • Downstream synthetic route of [ 151-10-0 ]

[ 151-10-0 ] Synthesis Path-Upstream   1~73

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Reference: [1] Angewandte Chemie - International Edition, 2011, vol. 50, # 2, p. 519 - 522
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YieldReaction ConditionsOperation in experiment
92% With carbon tetrabromide; anthraquinone-2-carboxylic acid In ethanol at 20℃; for 63 h; Irradiation General procedure: A pyrex test tube containing solid of 1,3,5-trimethoxybenzene (1a, 0.3 mmol), carbon tetrabromide (0.075 mmol), AQN-2-CO2H (0.03 mmol) and dry EtOH (5 mL) was irradiated for 20 h at roomtemperature with stirring by a 21W fluorescent lamp under air. The reactionmixture was concentrated in vacuo, quenched with aq Na2S2O3 and extractedwith EtOAc. The organic layer was dried over MgSO4 and concentrated invacuo. Purification of the residue by flash chromatography on silica gel(hexane/ethyl acetate = 6:1) provided 2-bromo-1,3,5-trimethoxybenzene (2a)(66.8 mg, 90percent,) as a white solid.
77% With N-Bromosuccinimide; chloro-trimethyl-silane In acetonitrile at 20℃; for 1 h; General procedure: To a solution of 4-bromoanisole (200.8 mg, 1.09 mmol, 1.0 equiv) in acetonitrile (2 mL) was added N-chlorosuccinimide(NCS) (158.3 mg, 1.19 mmol, 1.1 equiv) at rt to give a slightly cloudy mixture. Chlorotrimethylsilane (TMSCl) (14 μL, 0.11 mmol, 0.1 equiv) was then added drop-wise to the reaction mixture. Within a few minutes, the reaction mixture became clear pale yellow solution. The mixture continued to stir at rt for 1 h and was diluted with hexane. The biphasic mixture was concentrated on a rotary evaporator to a crude white solid-oil mixture. This mixture was taken up in hexane and filtered through a short plug of SiO2 and eluted with 5-10percent EtOAc-hexane solution. The clear filtrate was concentrated to obtain a mixture of 4-bromo-2-chloro-1-methoxybenzene (2a-Cl) and 2,4-dichloro-1-methoxybenzene (2a-diCl) 237.0 mg (88percent of 2a-Cl and 11percent of 2a-diCl,based on NMR ratio 2a-Cl: 2a-diCl = 7.1: 1.0; as a pale yellow solid).
77% at 80℃; for 24 h; Sealed tube General procedure: 1 mL [Bmim]NO3, 0.5 mmolsubstrate and 0.25 mmol Br2 were added to a dried 45 mL tube equipped witha magnetic stirring (note: the air in the tube was not removed). Then thereaction tube was sealed to perform the reaction at 80 C for 24 h. Once thereaction time was reached, the mixture was cooled to room temperature and3 mL water was added. Then the desired product was extracted with CH2Cl2(3 10 mL). GC analysis of the mixture provided the GC yield of the product.The product in another parallel experiment was purified by columnchromatography, and identified by 1H NMR and 13C NMR.
73 %Chromat. With carbon dioxide; oxygen; lithium bromide; copper(ll) bromide In water at 100℃; for 12 h; Autoclave; Green chemistry General procedure: A mixture of substrate (1 mmol), CuBr2 (22.4 mg, 10 molpercent), LiBr (130.3 mg, 1.5 equiv.), and 0.05 mL of water was placed in a 50 mL stainless steel autoclave equipped with an inner glass tube in room temperature. CO2 (4 MPa) and O2 (1 MPa) were subsequently introduced into the autoclave and the system was heated under the predetermined reaction temperature for 15 min to reach the equilibration. Then the final pressure was adjusted to the desired pressure by introducing the appropriate amount of CO2. The mixture was stirred continuously for the desired reaction time. After cooling, products were diluted with acetone and analyzed by gas chromatograph (Shimadzu GC-2014) equipped with a capillary column (RTX-17 30 m × 25 μm and RTX-wax 30 m × 25 μm) using a flame ionization detector by comparing the retention times of authentic samples. The residue was purified by column chromatography on silica gel (200–300 mesh, eluting with petroleum ether/ethyl acetate from petroleum ether to 50:1) to afford the desired product. The isolated products were further identified with NMR spectra (Bruker 400 MHz) and GC–MS or GCD, which are consistent with those reported in the literature.
95 %Spectr. With sulfuric acid; C22H24CuN4O3; oxygen; lithium bromide In acetonitrile at 70℃; for 24 h; A reaction flask was loaded with 33 m-(MeO)2C6H4 (0.3mmol), 34 LiBr (0.45mmol), Cu complex (5molpercent) and 67 H2SO4 (0.3mmol) in 19 CH3CN (0.5mL). The mixture was heated at 70°C under oxygen atmosphere for 24h. The product yields were determined by 1H NMR integration with the use of methylsulfone as the internal standard in 68 CDCl3.

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[4] Canadian Journal of Chemistry, 2009, vol. 87, # 2, p. 440 - 447
[5] Tetrahedron Letters, 1997, vol. 38, # 25, p. 4415 - 4416
[6] Tetrahedron Letters, 2004, vol. 45, # 25, p. 4887 - 4890
[7] Phosphorus, Sulfur and Silicon and the Related Elements, 2005, vol. 180, # 5-6, p. 1235 - 1240
[8] Organic Letters, 2017, vol. 19, # 16, p. 4243 - 4246
[9] Green Chemistry, 2018, vol. 20, # 19, p. 4448 - 4452
[10] Journal of the American Chemical Society, 2006, vol. 128, # 22, p. 7176 - 7178
[11] Synthetic Communications, 2001, vol. 31, # 19, p. 2955 - 2963
[12] Russian Journal of Organic Chemistry, 2007, vol. 43, # 9, p. 1282 - 1284
[13] Canadian Journal of Chemistry, 2009, vol. 87, # 12, p. 1675 - 1681
[14] Advanced Synthesis and Catalysis, 2009, vol. 351, # 11-12, p. 1925 - 1932
[15] Bulletin of the Korean Chemical Society, 2012, vol. 33, # 8, p. 2619 - 2622
[16] Organic Letters, 2015, vol. 17, # 12, p. 2886 - 2889
[17] Chemistry - A European Journal, 2015, vol. 21, # 34, p. 11976 - 11979
[18] Journal of Organic Chemistry, 2018, vol. 83, # 2, p. 930 - 938
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[21] Organic and Biomolecular Chemistry, 2017, vol. 15, # 13, p. 2804 - 2808
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[26] Advanced Synthesis and Catalysis, 2018, vol. 360, # 4, p. 626 - 630
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[31] Organic Letters, 2013, vol. 15, # 9, p. 2108 - 2111
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[33] Synlett, 2014, vol. 25, # 12, p. 1769 - 1775
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[37] Justus Liebigs Annalen der Chemie, 1944, vol. 556, p. 1,7
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[42] Patent: US4457875, 1984, A,
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YieldReaction ConditionsOperation in experiment
17% With silver carbonate; copper(ll) bromide; palladium dichloride In tetrahydrofuran at 110℃; for 24 h; General procedure: A mixture of carboxylic acid (1 equiv., 0.5 mmol), CuBr2 or CuCl2 (2 equiv., 1 mmol), Ag2CO3 (1 equiv., 0.5 mmol) and PdCl2 (0.1 equiv.) was heated inTHF (3 mL) under reflux at 110 oC for 24 h. After the reaction finished, the mixture was evaporated under vacuum and purified by columnchromatography to afford the desired product.
Reference: [1] Tetrahedron Letters, 2013, vol. 54, # 24, p. 3079 - 3081
[2] Tetrahedron Letters, 2013, vol. 54, # 24, p. 3079 - 3081
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YieldReaction ConditionsOperation in experiment
50 % de With tetrapropylammonium nonabromide In dichloromethane at 0℃; for 0.0833333 h; Inert atmosphere General procedure: A 0.66 M Pr4NBr9 in CH2Cl2 solution was prepared as described in General Procedure A. A 10-mL round-bottom flask equipped witha magnetic stir bar was charged with CH2Cl2 (1 mL) and the desired substrate (2 mmol). This solution was cooled to 0 °C and the Pr4NBr9 solution (0.75 mL, 25 molpercent) was added dropwise. The mixture was allowed to warm to r.t. and stirred for the reported time. Then the reaction was quenched and worked up as described in General Procedure A.
80 %Spectr. With sulfuric acid; C20H21BrCuN4O; oxygen; lithium bromide In acetonitrile at 70℃; for 24 h; A reaction flask was loaded with 33 m-(MeO)2C6H4 (0.3mmol), 34 LiBr (0.45mmol), Cu complex (5molpercent) and 67 H2SO4 (0.3mmol) in 19 CH3CN (0.5mL). The mixture was heated at 70°C under oxygen atmosphere for 24h. The product yields were determined by 1H NMR integration with the use of methylsulfone as the internal standard in 68 CDCl3.
Reference: [1] Tetrahedron Letters, 2004, vol. 45, # 25, p. 4887 - 4890
[2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1987, p. 1423 - 1428
[3] Tetrahedron Letters, 2004, vol. 45, # 25, p. 4887 - 4890
[4] Organic Letters, 2013, vol. 15, # 9, p. 2108 - 2111
[5] Synthesis (Germany), 2014, vol. 46, # 6, p. 740 - 747
[6] Journal of Organometallic Chemistry, 2018, vol. 859, p. 52 - 57
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Reference: [1] Chemical Communications, 2012, vol. 48, # 25, p. 3127 - 3129
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  • [ 20469-63-0 ]
Reference: [1] Tetrahedron Letters, 2012, vol. 53, # 41, p. 5555 - 5558
[2] Tetrahedron Letters, 2012, vol. 53, # 41, p. 5555 - 5558
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Reference: [1] Tetrahedron Letters, 1996, vol. 37, # 47, p. 8609 - 8612
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Reference: [1] Chemical Communications, 2012, vol. 48, # 25, p. 3127 - 3129
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Reference: [1] Rev. Fac. Cienc. quim. Univ. La Plata, 1950, vol. 25, p. 49,52
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Reference: [1] Tetrahedron Letters, 1988, vol. 29, # 51, p. 6715 - 6718
[2] Tetrahedron Letters, 1988, vol. 29, # 51, p. 6715 - 6718
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Reference: [1] Tetrahedron, 1982, vol. 38, # 8, p. 1105 - 1112
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Reference: [1] Patent: US2694729, 1951, ,
  • 13
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  • [ 13330-65-9 ]
Reference: [1] Organic Letters, 2013, vol. 15, # 13, p. 3484 - 3486
[2] Synthesis, 1983, # 12, p. 1046 - 1048
[3] Letters in Organic Chemistry, 2009, vol. 6, # 7, p. 585 - 587
[4] Angewandte Chemie - International Edition, 2012, vol. 51, # 29, p. 7275 - 7278
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YieldReaction ConditionsOperation in experiment
71%
Stage #1: With n-butyllithium In diethyl ether; hexane at -35℃; for 30 h;
Stage #2: With iodine In diethyl ether at 20℃; for 24 h;
To a solution of 1,3-dimethoxybenzene (25 g, 180 mmol) in diethyl ether (150 mL) was slowlyadded butyllithium (112.5 mL of 1.6 M solution in hexanes, 180 mmol). The reaction was stirred for30 h and then cooled to -35°C. Iodine (45.7 g, 180 mmol) was added and the reaction was stirredfor 24 h at 20°C and then poured into 10percent chloridric acid (60 mL). The aqueous phase wasseparated and extracted with ethyl acetate (2 × 60 mL) and the combined organic extracts washedwith saturated aqueous sodium thiosulfate (60 mL), brine (60 mL), dried over sodium sulfate,filtered and concentrated in vacuo. The product was purified by crystallization (diethylether) to give 16 (34g, 71percent) as a white solid; mp 105-106 °C (Lit.104 °C) [1] ; 1H NMR (CDCl3): δ 3.80 (s, 6H),6.43 (d, J 8.4, 2H), 7.17 (t, J 8.4, 1H); 13C NMR (CDCl3): δ 56.6, 76.3, 103.9, 129.8, 159.5; Anal.Calcd for C8H9IO2: C, 36.39; H, 3.44; Found: C, 36.40; H, 3.46.
66% With n-butyllithium; iodine In tetrahydrofuran; hexane at 0 - 20℃; Inert atmosphere (1) Synthesis of intermediate 2 2,6-Dimethoxybenzene 1(50 g, 0.36 mol) was dissolved in absolute THF (500 ml). A solution of n-butyl lithium in n-hexane (166 ml, 0.42 mol) was slowly added thereto at 0°C under the nitrogen atmosphere. To the resultant solution, a solution of iodine (96.5 g, 0.38 mol) dissolved in absolute THF (200 ml) was added dropwise at 0°C over 40 minutes. The resultant solution was stirred at room temperature overnight. After completion of stirring, methanol (80 ml) was added dropwise, and the resultant mixture was concentrated under the reduced pressure, and after adding water (200 ml), the mixture was extracted with ethyl acetate (250 ml) 3 times. Organic layers were combined, and said organic layer was washed with Na2S2O3 and brine, and then dried using sodium sulfate. After drying, inorganic salt was filtered off, and the filtrate was concentrated under the reduced pressure, and the residue was washed with methanol (50 ml) 4 times and dried to obtain intermediate 2 as yellow solid. Yield: 63 g (percent yield: 66percent).
66% With n-butyllithium; iodine In tetrahydrofuran; hexane at 0 - 20℃; for 0.666667 h; Inert atmosphere 2,6dimethoxybenzene (B141, 50 g0.36mol) was dissolved in the drying THF (500 mL). Thenhexane solution (166 mL, 0.42 mol) of nbutyl lithium was gradually added here at 0 degreeC under a nitrogen atmosphere. It was dropped at it at 0 degree C, having covered [ of theiodine (96.5 g0.38mol) in which the drying THF (200 mL) was dissolved ] it over the solutionobtained here for 40 minutes. The obtained solution was stirred at the room temperature allnight. After condensing under decompression of the mixture obtained by dropping methanol(80 mL) after an end and adding water (200 mL), ethyl acetate (3x250 mL) extracted. After itcollected organic layers and Na S O and a salt solution washed the organic layer, it dried usingsodium sulfate.Mineral salt was filtered after drying and it condensed under decompression, and when residuewas washed 4 times and dried with methanol (50 mL), the 2,6dimethoxyiodobenzene (B142) was obtained as a yellow solid (63 g0.24mol, 66percent yield).
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[2] Journal of the American Chemical Society, 2007, vol. 129, # 49, p. 15102 - 15103
[3] Organic and Biomolecular Chemistry, 2007, vol. 5, # 15, p. 2433 - 2440
[4] Journal of the American Chemical Society, 2004, vol. 126, # 34, p. 10526 - 10527
[5] Journal of the American Chemical Society, 2007, vol. 129, # 7, p. 1921 - 1930
[6] Chemistry - A European Journal, 2015, vol. 21, # 5, p. 2241 - 2249
[7] Heteroatom Chemistry, 2003, vol. 14, # 4, p. 360 - 364
[8] European Journal of Medicinal Chemistry, 2017, vol. 126, p. 1034 - 1038
[9] Beilstein Journal of Organic Chemistry, 2014, vol. 10, p. 2071 - 2076
[10] Patent: EP2351761, 2011, A1, . Location in patent: Page/Page column 22-23
[11] Patent: JP5812764, 2015, B2, . Location in patent: Paragraph 0100
[12] Tetrahedron, 2007, vol. 63, # 11, p. 2391 - 2403
[13] Journal of the Chemical Society - Perkin Transactions 1, 1998, # 13, p. 2023 - 2029
[14] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1982, vol. 36, # 2, p. 135 - 136
[15] Journal of Medicinal Chemistry, 1988, vol. 31, # 7, p. 1466 - 1471
[16] Tetrahedron, 1993, vol. 49, # 47, p. 10843 - 10854
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Reference: [1] Journal of Organic Chemistry, 2003, vol. 68, # 24, p. 9510 - 9512
[2] Canadian Journal of Chemistry, 2005, vol. 83, # 10, p. 1808 - 1811
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Reference: [1] Journal of Organic Chemistry, 2017, vol. 82, # 18, p. 9367 - 9383
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Reference: [1] Journal of Organic Chemistry, 2017, vol. 82, # 18, p. 9367 - 9383
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  • [ 387-46-2 ]
Reference: [1] Journal of Fluorine Chemistry, 2015, vol. 179, p. 106 - 115
[2] Chemical Research in Toxicology, 2018,
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YieldReaction ConditionsOperation in experiment
52%
Stage #1: With n-butyllithium In diethyl ether; hexane for 4 h; Inert atmosphere
Stage #2: With bromine In diethyl ether; hexane at -50 - 20℃; for 2 h;
EXAMPLES Production Example (A) Synthesis of Intermediate (A) [Show Image] (A-1) Synthesis of 1-bromo-2,6-dimethoxybenzene In the atmosphere of argon, 19.3g of 1,3-dimethoxybenzene and 500 mL of anhydrous diethyl ether were placed in a flask. 105 mL (1.6M) of a hexane solution of n-butyllithium was added, and the resulting reaction solution was stirred with heating for 4 hours. After cooling to room temperature while stirring, the reaction solution was cooled to -50°C, followed by dropwise addition of 25g of bromine. Then, while heating the reaction solution to room temperature, stirring was conducted for 2 hours. Then, 300 mL of an aqueous 10percent sodium thiosulfate solution was added, and the resulting mixture was stirred for 1 hour. The reaction solution was extracted with ether, and an aqueous phase was removed, and then, an organic phase was washed with saturated saline. The organic phase was dried with magnesium sulfate and concentrated. Residues were purified by means of silica gel column chromatography. The resulting crystals were washed with hexane, whereby 17.9g (yield: 52percent) of white crystals of 1-bromo-2,6-dimethoxybenzene were obtained.
52%
Stage #1: With n-butyllithium In diethyl ether; hexane for 4 h; Heating; Inert atmosphere
Stage #2: With bromine In diethyl ether; hexane at -50 - 20℃; for 2 h;
Under an argon atmosphere 1,3-dimethoxy benzene (19.3g), was charged with anhydrous diethyl ether (500mL) to the flask, added 1.6M n-butyl lithium in hexane solution (105mL), the reaction solution was stirred for 4 hours under heating. After cooling to room temperature with continuous stirring, cooled to -50 ° C., was added dropwise bromine (25 g). The reaction solution was stirred for 2 hours while warming to room temperature. 10percent aqueous solution of sodium thiosulfate (300mL) added, and the mixture was stirred for 1 hour. The reaction solution was extracted with ether, after removing the aqueous layer, the organic layer was washed with saturated brine. The organic layer was dried over magnesium sulfate, concentrated, and the residue was purified by silica gel chromatography. The obtained crystals were washed with hexane to obtain Intermediate 14 (17.9g). The yield was 52percent.
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[3] Patent: EP2436679, 2012, A1, . Location in patent: Page/Page column 46
[4] Patent: JP2015/7036, 2015, A, . Location in patent: Paragraph 0234; 0236
[5] Helvetica Chimica Acta, 1990, vol. 73, # 1, p. 48 - 62
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[7] European Journal of Organic Chemistry, 2011, # 2, p. 341 - 354
[8] Patent: US2017/54086, 2017, A1, . Location in patent: Paragraph 0260
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YieldReaction ConditionsOperation in experiment
57% With n-butyllithium In diethyl ether; hexane; water REFERENCE EXAMPLE 3(1)
In a solution of 1,3-dimethoxybenzene (3.0 g, 21.7 mmol) dissolved in diethyl ether (90 ml), a 1.65M solution of n-butyl lithium in n-hexane (19.8 ml, 32.7 mmol of n-butyl lithium) was added at room temperature, and a reaction mixture was heated to reflux for 4 hours.
After cooling the reaction mixture to 0° C., a solution of carbon tetrabromide (15.8 g, 47.7 mmol) in diethyl ether (60 ml) was added to the mixture, and stirred at room temperature for 20 hours.
A small amount of water was added to the reaction mixture, and then the reaction mixture was diluted with ethyl acetate (90 ml).
The organic layer was washed with water and dried over anhydrous magnesium sulfate.
Thereafter, the solvent was evaporated off, and the residue was purified by column chromatography to obtain 1-bromo-2,6-dimethoxybenzene (2.70 g).
Yield, 57percent.
Elementary analysis: C8 H9 O2 Br Calculated: C, 44.23percent; H. 4.15percent Found: C, 44.02percent; H. 4.23percent.
Reference: [1] Patent: US5621129, 1997, A,
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Reference: [1] European Journal of Organic Chemistry, 2011, # 2, p. 341 - 354
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Reference: [1] European Journal of Organic Chemistry, 2011, # 2, p. 341 - 354
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Reference: [1] European Journal of Organic Chemistry, 2011, # 2, p. 341 - 354
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  • [ 151-10-0 ]
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  • [ 1267964-44-2 ]
Reference: [1] European Journal of Organic Chemistry, 2011, # 2, p. 341 - 354
  • 25
  • [ 811711-33-8 ]
  • [ 151-10-0 ]
  • [ 16932-45-9 ]
  • [ 1267964-61-3 ]
Reference: [1] European Journal of Organic Chemistry, 2011, # 2, p. 341 - 354
  • 26
  • [ 104514-49-0 ]
  • [ 151-10-0 ]
  • [ 16932-45-9 ]
  • [ 1267964-61-3 ]
Reference: [1] European Journal of Organic Chemistry, 2011, # 2, p. 341 - 354
  • 27
  • [ 151-10-0 ]
  • [ 17715-69-4 ]
  • [ 16932-45-9 ]
Reference: [1] Tetrahedron Letters, 1988, vol. 29, # 51, p. 6715 - 6718
[2] Tetrahedron Letters, 1988, vol. 29, # 51, p. 6715 - 6718
  • 28
  • [ 151-10-0 ]
  • [ 17715-69-4 ]
  • [ 16932-45-9 ]
  • [ 20469-65-2 ]
Reference: [1] Tetrahedron, 1982, vol. 38, # 8, p. 1105 - 1112
  • 29
  • [ 98-85-1 ]
  • [ 151-10-0 ]
  • [ 85-27-8 ]
  • [ 106552-08-3 ]
Reference: [1] Synlett, 2011, # 11, p. 1585 - 1591
  • 30
  • [ 1445-91-6 ]
  • [ 151-10-0 ]
  • [ 85-27-8 ]
  • [ 106552-08-3 ]
Reference: [1] Synlett, 2011, # 11, p. 1585 - 1591
  • 31
  • [ 616-38-6 ]
  • [ 108-46-3 ]
  • [ 150-19-6 ]
  • [ 496-73-1 ]
  • [ 20734-74-1 ]
  • [ 151-10-0 ]
Reference: [1] Journal of Catalysis, 2006, vol. 243, # 2, p. 376 - 388
  • 32
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  • [ 7051-16-3 ]
Reference: [1] Journal of Chemical Research, 2006, # 6, p. 366 - 368
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Reference: [1] Journal of Chemical Research, 2006, # 6, p. 366 - 368
[2] Bioscience, Biotechnology and Biochemistry, 2009, vol. 73, # 11, p. 2547 - 2548
  • 34
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  • [ 16932-45-9 ]
  • [ 20469-65-2 ]
Reference: [1] Tetrahedron, 1982, vol. 38, # 8, p. 1105 - 1112
  • 35
  • [ 151-10-0 ]
  • [ 99-96-7 ]
  • [ 41351-30-8 ]
Reference: [1] European Journal of Medicinal Chemistry, 2009, vol. 44, # 8, p. 3158 - 3165
[2] Archiv der Pharmazie, 2009, vol. 342, # 8, p. 476 - 483
[3] Chemical Biology and Drug Design, 2012, vol. 79, # 3, p. 360 - 367
[4] Bioscience, Biotechnology, and Biochemistry, 1992, vol. 56, # 9, p. 1506 - 1507
[5] Tetrahedron Letters, 1987, vol. 28, # 33, p. 3787 - 3790
  • 36
  • [ 151-10-0 ]
  • [ 7051-15-2 ]
YieldReaction ConditionsOperation in experiment
74% With 4-chloromorpholine; ammonium peroxydisulfate; tris(bipyridine)ruthenium(II) dichloride hexahydrate In acetonitrile for 16 h; Irradiation General procedure: In a 5mL crimp cap vial 0.25mmol of the respective substrate, together with 0.3mmol (1.2equiv) of the N-chloramine or NCS, 0.3mmol (1.2equiv) (NH4)2S2O8, and 2molpercent (0.005mmol) [Ru(bpy)3]Cl2×6H2O were dissolved in 2mL of MeCN/water 4:1. The reaction mixture was degassed by three cycles of freeze-pump-thaw and irradiated for 16h with blue LEDs (λmax=455nm). For GC analysis 500μL of the reaction mixture was added to 500μL of the standard solution (0.1M), anisole for dimethoxybenzene, toluene for anisole, mixed, filtered and submitted to GC analysis. For Tables 4 and 5: After the irradiation the internal standard (0.01mmol n-pentadecane) was added to the reaction and the reaction was immediately quenched with satd Na2CO3-solution and brine. The mixture was extracted with ethyl acetate and subjected to GC–FID analysis.
Reference: [1] Tetrahedron, 2016, vol. 72, # 48, p. 7821 - 7825
[2] Journal of the Chemical Society, Chemical Communications, 1995, # 6, p. 611 - 612
[3] Angewandte Chemie - International Edition, 2016, vol. 55, # 17, p. 5342 - 5345[4] Angew. Chem., 2016, vol. 128, p. 5428 - 5431,4
[5] Journal of Medicinal Chemistry, 1982, vol. 25, # 1, p. 36 - 44
[6] Patent: US4579981, 1986, A,
  • 37
  • [ 67-72-1 ]
  • [ 151-10-0 ]
  • [ 7051-15-2 ]
YieldReaction ConditionsOperation in experiment
71.5% With n-butyllithium In hexane; water To a solution of 1,3-dimethoxybenzene (13.8 g) in dry ether (50 ml, freshly distilled from sodium benzophenone ketyl) is added dropwise 2.4M n-butyllithium (50 ml) at 5° C. over five minutes.
After the addition is complete, the mixture is heated under reflux for two and one-half hours and then cooled to -2° C.
To the cooled mixture is added dropwise a solution of hexachloroethane (30.9 g) in dry ether (80 ml) over 23 minutes, during which time the reaction temperature increased to 14° C.
After this addition is complete, the reaction mixture is allowed to warm to room temperature and is stirred at room temperature overnight.
The reaction mixture is cooled to 5° C. and water (50 ml) is added.
The layers are separated and the ether layer is washed with water (50 ml).
The aqueous phase is extracted with ether (50 ml) and the combined organic extracts are dried over anhydrous magnesium sulfate, filtered and evaporated.
Recrystallization of the residue from hexane (60 ml) yields 2-chloro-1,3-dimethoxybenzene (12.3 g, 71.5percent), mp 71°-73° C. (reported mp 69°-71° C., P.
Kovacic and M. E. Kurtz, ibid. page 2465).
Reference: [1] Patent: US4579981, 1986, A,
  • 38
  • [ 116-16-5 ]
  • [ 151-10-0 ]
  • [ 7051-15-2 ]
YieldReaction ConditionsOperation in experiment
50% With n-butyllithium In hexane; water (e)
Hexachloroacetone Method
To a solution of 1,3-dimethoxybenzene (13.8 g) in dry ether (50 ml, freshly distilled from sodium benzophenone ketyl) is added dropwise 2.4M n-butyllithium (50 ml) at 5° C. over five minutes.
After the addition is complete, the mixture is heated under reflux for two and one-half hours and then cooled to -65° C.
To the cooled mixture is added dropwise a solution of hexachloroacetone (19.8 ml) in dry ether (50 ml) over one hour.
The reaction mixture is allowed to warm to 0° C. and after one hour, water (50 ml) is added and the combined aqueous phases are extracted with ether.
The combined ether fractions are dried over anhydrous magnesium sulfate and filtered.
The filtrate is washed with 15percent sodium sulfate solution, dried over anhydrous magnesium sulfate, filtered and evaporated.
Trituration of the residue with hexane (41 ml) affords 2-chloro-1,3-dimethoxybenzene (8.6 g, 50percent) as a gum.
The gas-liquid chromatogram of the gum showed that it contained predominantly the desired 2-chloro compound. STR1
Reference: [1] Patent: US4579981, 1986, A,
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  • [ 2785-97-9 ]
  • [ 151-10-0 ]
  • [ 7051-15-2 ]
Reference: [1] Patent: US4579981, 1986, A,
  • 40
  • [ 109-72-8 ]
  • [ 151-10-0 ]
  • [ 50375-04-7 ]
  • [ 7051-15-2 ]
Reference: [1] Zeitschrift fuer Naturforschung, B: Chemical Sciences, 1989, vol. 44, # 8, p. 911 - 916
  • 41
  • [ 151-10-0 ]
  • [ 50375-04-7 ]
  • [ 7051-15-2 ]
Reference: [1] Zeitschrift fuer Naturforschung, B: Chemical Sciences, 1989, vol. 44, # 8, p. 911 - 916
[2] Zeitschrift fuer Naturforschung, B: Chemical Sciences, 1989, vol. 44, # 8, p. 911 - 916
[3] Zeitschrift fuer Naturforschung, B: Chemical Sciences, 1989, vol. 44, # 8, p. 911 - 916
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  • [ 25245-27-6 ]
Reference: [1] Journal of Chemical Research, 2006, # 6, p. 366 - 368
[2] Organic Letters, 2013, vol. 15, # 1, p. 140 - 143
  • 43
  • [ 67-56-1 ]
  • [ 621-23-8 ]
  • [ 591-50-4 ]
  • [ 25245-27-6 ]
  • [ 151-10-0 ]
Reference: [1] Journal of Physical Organic Chemistry, 2007, vol. 20, # 4, p. 241 - 244
  • 44
  • [ 151-10-0 ]
  • [ 6496-89-5 ]
Reference: [1] Synthetic Communications, 2014, vol. 44, # 4, p. 540 - 546
  • 45
  • [ 68-12-2 ]
  • [ 151-10-0 ]
  • [ 16932-49-3 ]
YieldReaction ConditionsOperation in experiment
94%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 2 h;
Stage #2: at 0℃; for 2 h;
Stage #3: With 1,3-Diiodo-5,5-dimethyl-2,4-imidazolidinedione; ammonia In tetrahydrofuran; hexane; water at 0 - 20℃; for 2 h;
n-Butyllithium (1.67 M solution in hexane, 2.9 mL, 4.8 mmol) was added dropwise to a solution of 1,3-dimethoxybenzene (0.55 g, 4.0 mmol) in THF (5 mL) at 0 °C. After 2 h, DMF (0.34 mL, 4.4 mmol) was added to the mixture and the obtained mixture was stirred at 0 °C. After 2 h at the same temperature, aq NH3 (8 mL, 120 mmol) and DIH (0.91 g, 2.4 mmol) were added and the resulting mixture was stirred for 2 h at rt. The reaction mixture was quenched with satd aq Na2SO3 (15 mL) and was extracted with ether (3.x.20 mL). The organic layer was washed with brine and dried over Na2SO4 to provide 2,6-dimethoxybenzonitrile in over 80percent purity. The product was purified by a column chromatography on silica gel (Hexane/EtOAc=3:1) to give pure 2,6-dimethoxybenzonitrile in 94percent yield as a colorless solid.
Reference: [1] Tetrahedron, 2011, vol. 67, # 5, p. 958 - 964
[2] Synlett, 2010, # 10, p. 1562 - 1566
  • 46
  • [ 506-68-3 ]
  • [ 151-10-0 ]
  • [ 4107-65-7 ]
  • [ 16932-49-3 ]
Reference: [1] Chemical Communications, 2012, vol. 48, # 25, p. 3127 - 3129
  • 47
  • [ 151-10-0 ]
  • [ 16932-49-3 ]
Reference: [1] Tetrahedron, 1993, vol. 49, # 47, p. 10843 - 10854
  • 48
  • [ 19158-51-1 ]
  • [ 151-10-0 ]
  • [ 16932-49-3 ]
Reference: [1] Heterocycles, 1997, vol. 46, # 1, p. 443 - 450
  • 49
  • [ 505-14-6 ]
  • [ 151-10-0 ]
  • [ 16932-49-3 ]
Reference: [1] Justus Liebigs Annalen der Chemie, 1967, vol. 709, p. 63 - 69
  • 50
  • [ 151-10-0 ]
  • [ 2734-70-5 ]
Reference: [1] Journal of Organic Chemistry, 2015, vol. 80, # 5, p. 2545 - 2553
[2] Tetrahedron Letters, 1984, vol. 25, # 4, p. 429 - 432
[3] Tetrahedron Letters, 1982, vol. 23, # 7, p. 699 - 702
[4] Journal of the American Chemical Society, 2017, vol. 139, # 33, p. 11622 - 11628
  • 51
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  • [ 2734-70-5 ]
  • [ 2735-04-8 ]
Reference: [1] Chemistry - A European Journal, 2017, vol. 23, # 3, p. 563 - 567
  • 52
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  • [ 151-10-0 ]
  • [ 2734-70-5 ]
  • [ 77422-78-7 ]
Reference: [1] Journal of the American Chemical Society, 1981, vol. 103, # 9, p. 2483 - 2485
  • 53
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  • [ 63624-28-2 ]
Reference: [1] Journal of the American Chemical Society, 1940, vol. 62, p. 603
[2] Journal of Medicinal Chemistry, 1977, vol. 20, # 10, p. 1235 - 1239
[3] Journal of Medicinal Chemistry, 2017, vol. 60, # 3, p. 1142 - 1150
[4] Patent: WO2018/95260, 2018, A1,
  • 54
  • [ 121-43-7 ]
  • [ 151-10-0 ]
  • [ 23112-96-1 ]
YieldReaction ConditionsOperation in experiment
90%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -40 - 30℃; for 1 h; Inert atmosphere
Stage #2: at -40 - -30℃; for 1 h;
Stage #3: With hydrogenchloride In tetrahydrofuran; hexane; water at 20 - 30℃; for 1 h;
41.5g (0.3mol) 1,3-dimethoxybenzene, 170gTHF are placed into a dry 1L three-necked flask. Under nitrogen protection, stirwhile cooling the system temperature to -30 ~ -40 deg.C. Add dropwise 240ml (0.6mol) n-butyllithium n-hexane solution. Dropping complete. Heat to 10 ~ 30 deg.C and maintain temperature for 1h. After maintaining the temperature, cool the system temperature to -30 ~ -40 deg.C. Add dropwise 62.4g (0.6mol)of trimethyl borate. Dropping complete. Maintain temperature for 1h. Maintain temperature was complete. Add 148g concentrated hydrochloric acid and 150g water. Reaction solution was stirred at 20 ~ 30 deg,C and maintain temperature 1h. Maintain temperature was completed, the reaction solution under reduced pressure until solvent-free solvent removal, the product was added to 200g of water, stirred for 20min, suction filtration using a Buchner funnel to give 45g of white solid, a yield of 90.0percent, measured by gas chromatographic purity of 99.0percent .
70%
Stage #1: With n-butyllithium In tetrahydrofuran at 0℃; for 4 h; Inert atmosphere
Stage #2: at -78 - 20℃; for 12 h; Inert atmosphere
It fills with nitrogen to a dried 5L reactor.1,3-dimethoxybenzene 200.0g (1.45 mol), put into a 2000ml tetrahydrofuran and lower to 0 .1.6M n-butyl lithium 1085ml (1.74 mol) of After slowly dropped trim and stirred for 4 hours at 0 °C. After raising to -78 °C After the temperature was reduced to trimethyl borate was added dropwise 225.6g (2.17 mol) slowly at room temperature and stirred 12 hours.After the reaction was completed, the mixture was stirred for 30 minutes at room temperature was added dropwise a 2M hydrochloric acid solution 1000ml. After extraction with ethyl acetate and water and the organic layer was concentrated under reduced pressure and recrystallized from ethyl acetate and hexane to obtain 184 g of a compound represented by Formula 1-a]. (70percent yield)
69%
Stage #1: With n-butyllithium In tetrahydrofuran at -10℃; for 4 h; Inert atmosphere
Stage #2: at -78 - 20℃;
Stage #3: With hydrogenchloride In waterInert atmosphere
Intermediate 1-b was synthesized as illustrated in the following Reaction Scheme 2: In a well-dried 2-L round-bottom flask reactor, 1,3-dimethoxy benzene (100.0 g, 0.724 mol) was dissolved in tetrahydrofuran (800 ml). The solution was chilled to −10° C. in a nitrogen atmosphere and then added slowly with drops of n-butyl lithium (543 ml, 0.868 mol). After 4 hrs of stirring at the same temperature, the temperature was decreased to −78° C. While this temperature was maintained, drops of trimethyl borate (112.8 g, 1.086 mol) were slowly added over 30 min, followed by stirring overnight at room temperature. After completion of the reaction, 2 N HCl was dropwise added for acidification. Extraction was made with water and ethyl acetate, and the organic layer thus formed was dried over magnesium sulfate. Subsequent to vacuum concentration, crystallization was conducted in heptane. The solid thus formed was filtered and washed with heptane to afford . 92.0 g, 69percent)
19 g
Stage #1: With n-butyllithium In tetrahydrofuran at -50℃; for 0.5 h; Inert atmosphere
Stage #2: With 1,4,7,10-tetramethyl-1,4, 7,10-tetraazacyclododecane In tetrahydrofuran at -50 - 20℃; for 4 h;
Stage #3: With hydrogenchloride In tetrahydrofuran; water for 1 h;
Under a nitrogen atmosphere, 250 g of anhydrous tetrahydrofuran was added to the reaction flask, stirring was continued, 19 g of 1,3-dimethoxybenzene was added and cooled to -50 ° C.N-BuLi was slowly added dropwise to 80 mL of 2.0 M, and after stirring for 30 minutes, 14 g of 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane was slowly added dropwise.After incubation for 2 hours, 30 mL of trimethyl borate was slowly added dropwise at -50 ° C, stirred for 1 hr, slowly rose to room temperature and stirred for 1 hour.And 200 g of concentrated hydrochloric acid was added thereto, followed by stirring for 1 hour to carry out a hydrolysis reaction.The layers were allowed to stand, and the organic layer was washed three times with water (3 x 50 g).The aqueous layers were combined and the aqueous layer was extracted once with 50 ml of petroleum ether. The combined organic layers were dried over 50 g of anhydrous sodium sulfate and filtered.The filtrate was concentrated to dryness to give 19 g of 2,6-dimethoxybenzeneboronic acid.

Reference: [1] Patent: WO2004/24738, 2004, A1, . Location in patent: Page/Page column 13-14
[2] Patent: CN105348240, 2016, A, . Location in patent: Paragraph 0059; 0060
[3] Organic and Biomolecular Chemistry, 2016, vol. 14, # 20, p. 4664 - 4668
[4] Organic Letters, 2012, vol. 14, # 16, p. 4250 - 4253
[5] Patent: KR2016/90242, 2016, A, . Location in patent: Paragraph 0162; 0163; 0164; 0165; 0166; 0167; 0168
[6] Patent: US2018/9776, 2018, A1, . Location in patent: Paragraph 0097-0098
[7] Bulletin de la Societe Chimique de France, 1973, p. 767 - 769
[8] Patent: CN102718785, 2016, B, . Location in patent: Paragraph 0044; 0045
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  • [ 151-10-0 ]
  • [ 23112-96-1 ]
Reference: [1] Journal of Organic Chemistry, 2003, vol. 68, # 8, p. 3238 - 3240
[2] Journal of the American Chemical Society, 2010, vol. 132, # 2, p. 777 - 790
[3] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 14, p. 4574 - 4581
[4] Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 6, p. 2051 - 2066
[5] Tetrahedron, 2008, vol. 64, # 2, p. 328 - 338
[6] European Journal of Organic Chemistry, 2002, # 19, p. 3294 - 3303
[7] Beilstein Journal of Organic Chemistry, 2014, vol. 10, p. 814 - 824
  • 56
  • [ 121-43-7 ]
  • [ 7732-18-5 ]
  • [ 151-10-0 ]
  • [ 23112-96-1 ]
YieldReaction ConditionsOperation in experiment
69%
Stage #1: With n-butyllithium In tetrahydrofuran at -10℃; for 4 h; Inert atmosphere
Stage #2: at -78 - 20℃;
1,3-dimethoxybenzene (100.0 g, 0.724 mol) was added to a dry 2 L round bottom flask reactor and 800 ml of tetrahydrofuran was added and melted.After cooling the reaction solution to -10 ° C under nitrogen atmosphere, n-butyllithium (543 ml, 0.868 mol) was slowly added dropwise.After stirring at the same temperature for 4 hours, the mixture was cooled to -78 ° C. The same temperature was maintained and trimethyl borate (112.8 g, 1.086 mol) was slowly added dropwise for 30 minutes, after which it was stirred overnight at room temperature.After completion of the reaction, 2N hydrochloric acid was slowly added dropwise and acidified. Water was extracted with magnesium sulfate after extraction and separation of the organic layer with water and ethyl acetate.The material was concentrated under reduced pressure and then crystallized using heptane. The resulting solid was filtered and washed with heptane to obtain intermediate 1-b (92.0 g, 69percent).
Reference: [1] Patent: CN107207454, 2017, A, . Location in patent: Paragraph 0441; 0447; 0448; 0450; 0451
  • 57
  • [ 5419-55-6 ]
  • [ 151-10-0 ]
  • [ 23112-96-1 ]
YieldReaction ConditionsOperation in experiment
20 g
Stage #1: With n-butyllithium In tetrahydrofuran at -30℃; for 0.5 h; Inert atmosphere
Stage #2: With N,N',N''-trimethyl-1,4,7-triazacyclononane In tetrahydrofuran at -30 - 20℃; for 4 h;
Stage #3: With hydrogenchloride In tetrahydrofuran; water for 1 h;
Under a nitrogen atmosphere, 250 g of anhydrous tetrahydrofuran was added to the reaction flask, stirring was continued, 19 g of 1,3-dimethoxybenzene was added and cooled to -50 ° C.N-BuLi was slowly added dropwise to 80 mL of 2.0 M, and after stirring for 30 minutes, 14 g of 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane was slowly added dropwise.After incubation for 2 hours, 30 mL of trimethyl borate was slowly added dropwise at -50 ° C, stirred for 1 hr, slowly rose to room temperature and stirred for 1 hour.And 200 g of concentrated hydrochloric acid was added thereto, followed by stirring for 1 hour to carry out a hydrolysis reaction.The layers were allowed to stand, and the organic layer was washed three times with water (3 x 50 g).The aqueous layers were combined and the aqueous layer was extracted once with 50 ml of petroleum ether. The combined organic layers were dried over 50 g of anhydrous sodium sulfate and filtered.The filtrate was concentrated to dryness to give 19 g of 2,6-dimethoxybenzeneboronic acid.
Reference: [1] Patent: US6593480, 2003, B2,
[2] Patent: CN102718785, 2016, B, . Location in patent: Paragraph 0046; 0047
[3] Patent: US2001/41802, 2001, A1,
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  • [ 23112-96-1 ]
Reference: [1] Patent: US6521666, 2003, B1,
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Reference: [1] Patent: TW2017/22896, 2017, A,
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  • [ 151-10-0 ]
  • [ 102503-23-1 ]
Reference: [1] Tetrahedron Letters, 1990, vol. 31, # 29, p. 4229 - 4232
[2] Tetrahedron Letters, 1990, vol. 31, # 29, p. 4229 - 4232
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Reference: [1] Phosphorus and Sulfur and the Related Elements, 1983, vol. 14, p. 189 - 210
[2] Journal of Chemical Research, Miniprint, 1985, # 2, p. 467 - 490
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  • [ 103068-41-3 ]
Reference: [1] Canadian Journal of Chemistry, 1988, vol. 66, p. 1479 - 1482
[2] Canadian Journal of Chemistry, 1988, vol. 66, p. 1479 - 1482
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  • [ 117902-15-5 ]
Reference: [1] Canadian Journal of Chemistry, 1988, vol. 66, p. 1479 - 1482
  • 64
  • [ 151-10-0 ]
  • [ 59870-68-7 ]
Reference: [1] Synthetic Communications, 2014, vol. 44, # 4, p. 540 - 546
[2] Synthetic Communications, 2014, vol. 44, # 4, p. 540 - 546
[3] Synthetic Communications, 2014, vol. 44, # 4, p. 540 - 546
[4] Synthetic Communications, 2014, vol. 44, # 4, p. 540 - 546
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  • [ 192182-54-0 ]
Reference: [1] Organic Letters, 2007, vol. 9, # 5, p. 761 - 764
[2] Angewandte Chemie - International Edition, 2011, vol. 50, # 2, p. 519 - 522
  • 66
  • [ 73183-34-3 ]
  • [ 151-10-0 ]
  • [ 365564-07-4 ]
YieldReaction ConditionsOperation in experiment
99% at 100℃; for 16 h; Inert atmosphere The Examples milligrams Preparation of 3,5-dimethoxybenzene boronic acid pinacol ester, specifically including the steps of: nitrogenEnvironment, the reaction flask was added 1,3-dimethoxybenzene (69.1mg, 0.5mmol),CoupletBoronic acid pinacol ester(126.9mg, 0.5mmol, of formula (5)),Methoxy-1,5-cyclooctadiene iridium dimer(3.4mg, 0.005mmol, 1percent, formula (6)),Borane pyridine ligands ago(4.0mg, 0.01mmol, 2percent, of Formula (1))And cyclopentyl methyl ether(1mL, 1,3-dimethoxybenzene reaction concentration is 0.5mol / L),The reaction at 100 16h; the reaction was completed by rotary evaporation (20 ~ 40 ) removing the solvent (cyclopentyl methyl ether), was purified by columnChromatography (using 200-300 mesh size silica gel, substance to be purified by silica gel ratio of 50 to 100: 1, eluent stoneOleyl ether and ethyl acetate, the volume ratio 20 ~ 50: 1) to afford the product to give a colorless 3,5-dimethoxybenzene boronic acid pinacol ester solid(125mg, 99percent),
68.4% With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In cyclohexane at 20℃; Inert atmosphere 1523.6 mg (6 mmol) of pinacol diboronate (B2pin2), 132.6 mg of [Ir (0 Torr) (COD)] and 107.4 mg (0.30 mmol) of 4,4-di-tert-butyl linkage Into 15 mL of cyclohexane, add dtbpy, protect with N2, stir at room temperature, and add 1.22 mL of 1,3-dimethoxybenzene while stirring. Stir the reaction for 10 h. Evaporate the solvent and purify by column chromatography. Petroleum ether: Elution with ethyl acetate (V:V=5:1), dried to give 1083.4 mg of compound 3 with a yield of 68.4percent.
Reference: [1] Patent: CN104725409, 2016, B, . Location in patent: Paragraph 0036; 0037; 0040
[2] Journal of the American Chemical Society, 2015, vol. 137, # 25, p. 8058 - 8061
[3] Research on Chemical Intermediates, 2013, vol. 39, # 4, p. 1917 - 1926
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[5] Chemistry - A European Journal, 2017, vol. 23, # 26, p. 6282 - 6285
[6] Patent: CN108003001, 2018, A, . Location in patent: Paragraph 0027; 0034
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[12] Tetrahedron Letters, 2010, vol. 51, # 20, p. 2690 - 2692
[13] Journal of the American Chemical Society, 2010, vol. 132, # 33, p. 11389 - 11391
[14] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 2, p. 861 - 864
[15] Organic Letters, 2010, vol. 12, # 24, p. 5700 - 5703
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YieldReaction ConditionsOperation in experiment
36%
Stage #1: With n-butyllithium In tetrahydrofuran at 0 - 20℃; for 3.5 h;
Stage #2: at 0℃; for 0.5 h;
To a solution of 1,3-dimethoxybenzene (2 ml, 15.30 mmol) in anhydrous THF (35 ml) at 0° C., nBuLi (6.2 ml, 15.50 mmol) is added to the dropping funnel for 5 min.
The reaction medium is stirred at room temperature for 3.5 h, then 2-bromochlorobenzene (1.6 ml, 13.70 mmol) is added by syringe, dropwise, at 0° C., for 30 min.
After 15 min of stirring, the reaction medium is cooled to -78° C. and nBuLi (6.20 ml, 15.50 mmol) is added to the dropping funnel dropwise for 5 min.
After 30 min, chlorodicyclohexylphosphine (3.03 ml, 13.70 mmol) is added.
The reaction medium is maintained at -78° C. for 1 h, under rapid stirring (mechanical stirring).
After returning to room temperature, the precipitate obtained is filtered on a fritted disc containing silica topped with a layer of cellulose acetate, with 600 ml ethyl acetate.
The solvents are evaporated with a rotary evaporator, and the orange oil obtained is recrystallized in acetone to obtain S-Phos ligand in the form of white crystals with a yield of 36percent (1.22 g, 2.97 mmol).
MP: 163-165° C. (Lit.
MP 162.0-162.5° C.); TLC: (AcOEt/cyclohexane 10/90). Rf=0.65; 1H-NMR (CDCl3): δ=0.99-1.26 (m, 10H, H(Cy)), 1.60-1.77 (m, 12H, H(Cy)), 3.67 (s, 6H, Me), 6.58 (d, 2H, J=8.2 Hz, H3' and H5'), 7.15-7.18 (m, 1H, H(Ar)), 7.18-7.42 (m, 3H, H(Ar)), 7.57 (d, 1H, J=7.4 Hz, H(Ar)) ppm; 13C-NMR (CDCl3): δ=26.5, 27.3, 27.4, 27.6, 29.0, 29.1, 29.8, 30.1, 33.8, 34.0 (C(Cy)), 55.3 (Cb), 103.1 (Ca), 126.2, 128.2, 128.8 (C3', C4', C5'), 130.9, 131.00, 132.4, 135.8 (C3, C4, C5, C6), 135.8, 136.1, 142.7, 143.1, 157.4 (C2', C6') ppm; IR (KBr): υ=3000, 2923, 2851, 1588, 1471, 1442, 1428, 1108 cm-1.
Reference: [1] Patent: US2011/184059, 2011, A1, . Location in patent: Page/Page column 9
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Reference: [1] Journal of the American Chemical Society, 2014, vol. 136, # 24, p. 8568 - 8576
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Reference: [1] Journal of the American Chemical Society, 2018,
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