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Chemical Structure| 325142-82-3 Chemical Structure| 325142-82-3
Chemical Structure| 325142-82-3

4,4,5,5-Tetramethyl-2-(3-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane

CAS No.: 325142-82-3

4.5 *For Research Use Only !

Cat. No.: A114283 Purity: 98%

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Product Details of [ 325142-82-3 ]

CAS No. :325142-82-3
Formula : C13H16BF3O2
M.W : 272.07
SMILES Code : CC1(C)OB(OC1(C)C)C1=CC(=CC=C1)C(F)(F)F
MDL No. :MFCD05863925
InChI Key :GJNOCGLTCQPYAC-UHFFFAOYSA-N
Pubchem ID :2760604

Safety of [ 325142-82-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 325142-82-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 19
Num. arom. heavy atoms 6
Fraction Csp3 0.54
Num. rotatable bonds 2
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 67.92
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

18.46 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.0
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

3.79
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

4.16
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

2.68
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

2.87
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.7

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-4.02
Solubility 0.0262 mg/ml ; 0.0000963 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-3.87
Solubility 0.0366 mg/ml ; 0.000134 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-4.88
Solubility 0.00356 mg/ml ; 0.0000131 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

Yes
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

Yes
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.27 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

2.95

Application In Synthesis of [ 325142-82-3 ]

* 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 [ 325142-82-3 ]

[ 325142-82-3 ] Synthesis Path-Downstream   1~30

  • 1
  • [ 98-08-8 ]
  • [ 25015-63-8 ]
  • [ 325142-82-3 ]
  • [ 214360-65-3 ]
YieldReaction ConditionsOperation in experiment
General procedure: [RuCl2(p-cymene)]2 (2.3 mg, 3.8 mumol) and TpMe2K (2.5 mg, 7.5 mumol)were placed in a resealable Schlenk tube. The tube was evacuated,backfilled with dinitrogen and then charged with the arene 2 (5 mmol).After stirring the mixture at room temperature for 1 h, pinacolborane(1; 36 muL, 0.25 mmol) was added. The reaction mixture was thenstirred at 120 C for 16 h. After the reaction, the mixture was analysedby GC and GC-MS. The volatile material was removed in vacuo, andthe residue was purified by Kugelrohr distillation.
  • 2
  • [ 98-08-8 ]
  • [ 73183-34-3 ]
  • [ 325142-82-3 ]
  • [ 214360-65-3 ]
YieldReaction ConditionsOperation in experiment
With bis(1,5-cyclooctadiene)nickel (0); 1,3-bis(mesityl)imidazolium chloride; sodium t-butanolate; at 140℃; for 24h;Inert atmosphere; Glovebox; Sealed tube; General procedure: A 20-mL glass vessel equipped with J. Young O-ring tap containing a magnetic stirring bar was dried with a heat-gun under reduced pressure and filled with nitrogen after cooling to room temperature. After adding bis(pinacolato)diboron (127.0 mg, 0.5 mmol), the vessel was introduced inside an argon-atmosphere glovebox. In the glovebox, Ni(cod)2 (13.8 mg, 0.05 mmol) and CsF (19.0 mg, 0.125 mmol) were added to the vessel, which was sealed with O-ring tap and then taken out of the glovebox. Then, PCyp3 (23.8 mg, 0.1 mmol) and benzene derivative 1 (3.0 mL) were added to the vessel under nitrogen atmosphere. The vessel was heated at 140 C for 24 h in an oil bath with stirring. After cooling the reaction mixture to room temperature, the mixture was concentrated and directly purified by preparative thin-layer chromatography (PTLC; hexane/ethyl acetate as the eluent) to afford the borylation product 2. Yields of 2 are calculated based on bis(pinacolato)diboron.
  • 3
  • 2-chloro-3,4-dimethoxy benzonitrile [ No CAS ]
  • [ 325142-82-3 ]
  • 5,6-dimethoxy-3'-trifluoromethyl-2-cyano-biphenyl [ No CAS ]
  • 4
  • [ 401-81-0 ]
  • [ 25015-63-8 ]
  • [ 325142-82-3 ]
  • 5
  • [ 98-08-8 ]
  • 4,4,5,5-tetramethyl-1,3,2-dioxaborolane [ No CAS ]
  • [ 325142-82-3 ]
  • [ 214360-65-3 ]
  • 7
  • [ 76-09-5 ]
  • [ 1423-26-3 ]
  • [ 325142-82-3 ]
YieldReaction ConditionsOperation in experiment
47% In toluene; at 20℃; for 2h; The title compound (47%, oil) was prepared from 3-trifluoromethylphenylboronic acid and pinacol. 1H NMR (300 MHz, CDCl3): delta 1.35 (s, 12H), 7.48 (t, 1H), 7.70 (d, 1H), 7.97 (d, 1H), 8.06 (bs, 1H).
  • 8
  • [ 77295-66-0 ]
  • [ 325142-82-3 ]
  • [ 1008756-40-8 ]
  • 9
  • [ 98-08-8 ]
  • [ 73183-34-3 ]
  • [ 1073339-21-5 ]
  • [ 325142-82-3 ]
  • [ 214360-65-3 ]
  • 12
  • [ 98-08-8 ]
  • [ 73183-34-3 ]
  • [ 1197374-02-9 ]
  • [ 325142-82-3 ]
  • [ 214360-65-3 ]
  • 13
  • [ 591-50-4 ]
  • [ 325142-82-3 ]
  • [ 366-04-1 ]
  • 14
  • [ 98-16-8 ]
  • [ 73183-34-3 ]
  • [ 325142-82-3 ]
YieldReaction ConditionsOperation in experiment
70% With tert.-butylnitrite; dibenzoyl peroxide; In acetonitrile; at 20℃; for 4h; EXAMPLE 2 Synthesis of 4,4,5,5-tetramethyl-2-(3-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane B2pin2 (1.0 mmol, 254 mg), benzoyl peroxide (0.02 mmol, 5 mg), 3-F3CC6H4NH2 (1 mmol, 161 mg) and acetonitrile (3 mL) were added to a 25 mL tube-type reactor, followed by the addition of tert-butyl nitrite (1.5 mmol, 154 mg). The reaction was conducted at room temperature for 4 h. The solution'was concentrated after the reaction and the resultant was purified by column chromatography (eluted by petroleum ether:ethyl acetate=30:1, V:V) to give 4,4,5,5-tetramethyl-2-(3-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane having the following structure: This compound is colorless liquid and obtained in 70% yield. Its NMR data are as follows: 1NNMR (400 MHz, CDCl3) delta 8.09~8.06(m, 1H), 7.97 (d, 1H, J=7.4 Hz), 7.70 (d, 1H, J=7.9 Hz), 7.48 (t, 1H, J=7.7 Hz), 1.36(s, 12H); 13C NMR (100 MHz, CDCl3) delta 137.9, 131.4, 131.3, 131.3, 131.2, 130.2, 129.8, 129.8, 128.8, 128.0, 127.8, 127.7, 127.7, 127.7, 125.6, 122.9, 84.2, 24.8.
70% With tert.-butylnitrite; dibenzoyl peroxide; In acetonitrile; at 20℃; for 4h; B2pin2 (1.0 mmol, 254 mg), benzoyl peroxide (0.02 mmol, 5 mg), 3-F3CC6H4NH2 (1 mmol, 161 mg) and acetonitrile (3 mL) were added to a 25 mL tube-type reactor, followed by the addition of tert-butyl nitrite (1.5 mmol, 154 mg). The reaction was conducted at room temperature for 4 h. The solution was concentrated after the reaction and the resultant was purified by column chromatography (eluted by petroleum ether : ethyl acetate = 30:1, V:V) to give 4,4,5,5-tetramethyl-2-(3-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane having the following structure: This compound is colorless liquid and obtained in 70% yield. Its NMR data are as follows: 1H NMR (400MHz, CDCl3) delta 8.09~8.06(m, 1H), 7.97 (d, 1H, J=7.4Hz), 7.70 (d, 1H, J=7.9Hz), 7.48 (t, 1H, J=7.7Hz), 1.36(s, 12H); 13C NMR (100MHz, CDCl3) delta 137.9, 131.4, 131.3, 131.3, 131.2, 130.2, 129.8, 129.8, 128.8, 128.0, 127.8, 127.7, 127.7, 127.7, 125.6, 122.9, 84.2, 24.8.
  • 15
  • [ 33252-29-8 ]
  • [ 325142-82-3 ]
  • [ 833457-45-7 ]
  • 16
  • C13H14BrN5O [ No CAS ]
  • [ 325142-82-3 ]
  • [ 701243-97-2 ]
  • 17
  • [ 626-05-1 ]
  • [ 325142-82-3 ]
  • [ 180606-07-9 ]
YieldReaction ConditionsOperation in experiment
59% With sodium t-butanolate; In tetrahydrofuran; toluene; at 50℃; for 6h;Sealed tube; General procedure: 1-Chloro-4-iodobenzene (48 mg, 0.20 mmol), 48 mg, 0.20 mmol)1,1-Dibornathethane (2, 107 mg, 0.30 mmol) and sodium tert-butoxide base (38 mg, 0.40 mmol) were placed in a 4 mL vial. Toluene / tetrahydrofuran (2.0 mL, 1: 1 mixed solution) was then added.The vial was reacted for six hours at 80 C sealed with a PTFE / silicone coated cap.The reaction solution was filtered through celite with dichloromethane, and the organic material was concentrated under reduced pressure. The products were then separated and purified on silica gel column chromatography Phi 2.0 cm × 8 cm under the specified eluent conditions under n-hexane: diethyl ether, 10: 1 eluent. As a result 2- (4-Chlorophenyl) -4,4,5,5-tetramethyl-1,3,2-dioxaborolane boronated compound was produced. (32 mg, 67% yield); The procedure of Example 3 was followed except that aryl iodide was changed according to the following reaction formula (3), and the results are shown in Table 2.
171 mg In diethyl ether; at 20℃; for 4h; General procedure: To a solution of aniline (1 mmol) in 3 ml of distillated acetonitrile, at 0C, is added boron trifluoride etherate (1.5mmol 0.4 ml) and the solution is stirred for 5 minutes. Isoamyl nitrite (1.2 mmol, 0.2 ml) is then slowly added and thesolution is stirred for 15 minutes. Diisopropylamino borane (4 mmol, 0.6 ml) is then slowly added and the mixture isallowed to be stirred at room temperature for 3 hours. The reaction is then quenched, at 0C, by the slow addition of 2ml of distillated methanol and stirred 1 hour at room temperature. The mixture is concentrated under vacuum and asolution of pinacol (1.3 mmol, 153 mg) in 2 ml of diethyl ether is added and the mixture is stirred 4 hours at roomtemperature. 10 ml of diethyl ether is then added and the crude is washed three time with 6 ml of a aqueous solution of copper chloride (50 g/L). The organic phase is then filtered and died over Na2SO4 and concentrated under vacuum toafford pure aryl boronate. 113 mg of 2-(4-methoxy-phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane were obtained following the generalprocedure B using 123 mg of 4-methoxyaniline as a pale yellow oil, yield: 52.5%. 1H NMR (300 MHz, CDCl3) delta 7.75 (d, J= 8.7 Hz, 2H) 6.90 (d, J= 8.7 Hz, 2H) 3.83 (s, 3H) 1.33 (s, 12H). 11B NMR (100 MHz, CDCl3) delta 31.0513C NMR (75 MHz, CDCl3) deltaMS (EI) tR= 9.05 min; m/z: 234 (M+., 100%). 171 mg of 2-(3-trifluoromethylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane were obtained following the generalprocedure D according to example 3, using 260 mg of 3-trifluoromethylbenzenediazonium tetrafluoroborate as apale yellow oil.1H NMR (300 MHz, CDCl3) delta 7.97 (d, J = 7.4 Hz, 1H) 7.70 (d, J = 7.9 Hz, 1H) 7.48 (t, J = 7.6 Hz, 1H) 1.36 (s, 12H)11B NMR (100 MHz, CDCl3) delta 30.4813C NMR (75 MHz, CDCl3) delta 138.12; 128.16; 127.94; 118.30; 84.43; 25.02MS (EI) tR= 7.02 min; m/z: 272 (M+, 100%)
  • 19
  • [ 77-85-0 ]
  • [ 325142-82-3 ]
  • Na(3-(CF3)C6H4B(OCH2)3CCH3) [ No CAS ]
  • 20
  • [ 77-85-0 ]
  • [ 1310-73-2 ]
  • [ 325142-82-3 ]
  • Na(3-(CF3)C6H4B(OCH2)3CCH3) [ No CAS ]
  • 21
  • 2-bromo-1-iodo-3-methylbenzene [ No CAS ]
  • [ 325142-82-3 ]
  • [ 1319196-89-8 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 80℃; A solution of 2-bromo-l-iodo-3-methylbenzene (200 mg, 0.67 mmol), 4,4,5,5- tetramethyl-2-(3-(trifluoromethyl)phenyl)-l,3,2-dioxaborolane (220 mg, 0.81 mmol), sodium carbonate (214 mg, 2.02 mmol) and tetrakis(triphenylphophine) palladium (38.9 mg, 0.034 mmol) in toluene (2.0 mL)/EtOH (1.2 mL)/Water (0.2 mL) was heated in an oil bath at 80 C overnight. The reaction was concentrated and the resultant residue purified by column chromatography (100% Hexanes) to yield 2-bromo-3-methyl-3'- (trifluoromethyl)biphenyl.
  • 22
  • 2-bromo-1-iodo-3-methylbenzene [ No CAS ]
  • [ 325142-82-3 ]
  • [ 1319194-46-1 ]
  • 23
  • [ 1338718-15-2 ]
  • [ 325142-82-3 ]
  • [ 1338718-79-8 ]
YieldReaction ConditionsOperation in experiment
66.8% With potassium acetate; sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In water; acetonitrile; at 100℃; for 0.666667h;Microwave irradiation; Inert atmosphere; Step 1: Preparation of [(R)-1-(4-[5-tert-butoxycarbonylamino-2-(3-trifluoromethyl-phenyl)-thiazole-4-carbonyl]-amino}-2-methyl-2H-pyrazol-3-yl)-perhydro-azepin-4-yl]-carbamic acid benzyl ester In a microwave vial was placed ((R)-1-{4-[(2-bromo-5-tert-butoxycarbonylamino-thiazole-4-carbonyl)-amino]-2-methyl-2H-pyrazol-3-yl}-perhydro-azepin-4-yl)-carbamic acid benzyl ester (100.0 mg, 0.154 mmol), 4,4,5,5-tetramethyl-2-(3-trifluoromethyl-phenyl)-1,3,2-dioxaborolane (209.7 mg, 0.77 mmol, 5.0 eq.), sodium carbonate (49.0 mg, 0.46 mmol, 3.0 eq.), potassium acetate (45.4 mg, 0.46 mmol, 3.0 eq.), [1,1'-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), complexed with dichloromethane (1:1) (25.2 mg, 0.03, mmol, 0.20 eq), ACN (9.0 mL), and water (1.9 mL). The reaction mixture was degassed with N2 for 10 minutes and then subjected to microwave irradiation at 100 C. for 40 minutes. The reaction mixture was diluted with ethyl acetate (50 mL) and then filtered through a pad of Celite. The filtrate was washed with 50% brine/water, water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude was purified via flash column chromatography eluted with 50 to 100% ethyl acetate/heptane to give 73.5 mg (66.8%) of desired product as an oil. MS (ESI) m/z: 714.4 [M+H]+.
  • 24
  • [ 19063-55-9 ]
  • [ 325142-82-3 ]
  • [ 1337936-13-6 ]
  • 25
  • [ 401-81-0 ]
  • [ 73183-34-3 ]
  • [ 325142-82-3 ]
YieldReaction ConditionsOperation in experiment
81% With pyridine; cesium fluoride; In dimethyl sulfoxide; at 105℃; for 2h;Inert atmosphere; Schlenk technique; General procedure: An oven-dried Schlenk tube, containing a Teflon-coated magnetic stir bar was charged with CsF (228 mg, 1.5 mmol, 3 equiv) and bispinacolatodiboron (254 mg, 1 mmol, 2 equiv). Under an argon atmosphere, freshly distilled DMSO (0.4 mL), the appropriate aryl iodide (0.5mmol), and pyridine (0.4 to 1 equiv) were added successively. The reaction mixture was heated to 105 C and stirred for 2 h under argon.
59%Chromat. With copper(II) ferrite; potassium tert-butylate; In N,N-dimethyl-formamide; at 20℃; for 12h;Green chemistry; General procedure: 4-Iodoanisole (0.813 mmol, 200 mg), bis(pinacolato)diboron (1.219 mmol, 309 mg) were dissolved in 3 mL of dmf followed by copper ferrite nanoparticles (5mol% with respect to 4-iodoanisole) and potassiumtert-butoxide (1.219 mmol, 137 mg) were added to a 10 mLcapped vial and stirred at RT for time indicated. After stirring, the mixture was diluted with diethyl ether and filtered through celite bed. The filtrate was extracted with water (3 times) and the organic phase was dried over anhydrous MgSO4. The crude product was subjected to analyze by GC-MS. The conversion yield is accurately measured based on the consumption of 4-iodoanisole and the side product formed due to protodeiodination.
  • 27
  • [ 76-09-5 ]
  • C13H19BF3N [ No CAS ]
  • [ 325142-82-3 ]
  • 28
  • trifluoromethylsilver [ No CAS ]
  • [ 210907-84-9 ]
  • [ 325142-82-3 ]
YieldReaction ConditionsOperation in experiment
54% General procedure: An oven-dried Schlenk tube (A) equipped with a magnetic stir bar was charged with AgF (132.2 mg, 1.05 mmol, 3.5 equiv), sealed with a septum, and degassed by alternating vacuum evacuation and nitrogen backfill (three times) before freshly distilled EtCN (3 mL)was added. To the resulting suspension, which was precooled to -78 C (dry ice-acetone bath), was added TMSCF3 (149.3 mg, 1.05 mmol, 3.5 equiv) by microsyringe. The mixture was allowed towarm to r.t. and stirring was continued for an additional 15 min. In due course, AgF solid dissolved and a gray, dark solution of [Ag-CF3] formed. Another Schlenk tube (B) equipped with a magnetic stir bar was charged with the aniline (ArNH2; 0.30 mmol, 1.0 equiv) in freshly distilled EtCN (1.5 mL). To the resulting solution, which was precooled to 0 C (ice bath), aq HCl (12 M; 50.0 muL, 0.60mmol, 2.0 equiv) was added; precipitate formed immediately. After 5 min stirring, t-BuONO (37.7 mg, 0.33 mmol, 1.1 equiv) was added by microsyringe, and the mixture was allowed to stir at 0 C for 15 min. The resulting suspension in Schlenk tube (B) was degassed by alternating vacuum evacuation at -196 C (liquid nitrogen), then the solution was allowed to warm to r.t. under a nitrogen atmosphere (three times), and finally cooled to -78 C (dry ice-acetone bath). The gray, dark solution of [AgCF3] in Schlenk tube (A), which was precooled to -78 C (dry ice-acetone bath), was added to Schlenk tube (B) (ArN2+Cl-) by syringe at -78 C (dry ice-acetone bath) over a period of 1 h. After the addition was complete, the reaction mixture was stirred for 3 h at -78 C (dry ice-acetone bath), allowed to warm to r.t., and stirring was continued for an additional 1 h. An off-white precipitate was observed, and the reaction mixture was diluted with EtOAc (3 mL) and filtered through a short silica gel column. The solvent was removed under reduced pressure with a rotatory evaporator, and the crude residue was purified by silica gel column chromatography to give the desired trifluoromethylation product 3. The yields of products 3a, 3f, 3g, 3l, 3o, 3r, 3x, and 3zb are based on the 19F NMR spectra with 4-F3COC6H4OMe as internal standard. Analytical data for the representative product ethyl 4-(trifluoromethyl)benzoate (3i) are provided below. Data for other products can be found in the literature.
  • 29
  • [ 122918-25-6 ]
  • [ 325142-82-3 ]
  • [ 833457-45-7 ]
YieldReaction ConditionsOperation in experiment
90% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; for 4h;Reflux; Inert atmosphere; 2-bromo-6-cyanopyridine (0.50 g, 2.7 mmol), the colorless oily liquid of the preparation 1 (0.89 g, 3.3 mmol) and Pd(PPh3)4 (158 mg, 0.14 mmol) were added into a 100 ml single neck bottle, followed by adding THF (30 ml) and a potassium carbonate solution (potassium carbonate (0.94 g) in deionized water (7 ml)) to obtain a mixture. The mixture was heated under reflux for 4 hours under a nitrogen gas atmosphere. After the reaction was finished, the mixture was cooled to room temperature, followed by solvent removal by virtue of reduced pressure distillation to obtain a distilled mixture. Then, the distilled mixture was added with dichloromethane and water for extraction. The dichloromethane layer was collected and added with magnesium sulfate to remove water. The dichloromethane layer was then filtrated and the filtrate was collected. Next, the filtrate was concentrated by means of reduced pressure distillation to obtain a yellow solid product. The yellow solid product was subjected to column chromatography, in which a mixture of ethyl acetate and hexane(ethyl acetate: hexane=1:4) was used as an eluent. An eluate was collected followed by removing the eluent using a rotary evaporator. A white solid product was obtained (608 mg, 2.4 mmol, 90% yield. The spectrum analysis for the white solid product is: 1H NMR (400 MHz, CDCl3, 298K). delta(ppm): 8.27 (s, 1H), 8.22 (d, JHH=8.0 Hz, 1H), 8.02?7.90 (m, 2H), 7.76 ?7.59 (m, 3H).
  • 30
  • [ 401-78-5 ]
  • [ 61676-62-8 ]
  • [ 325142-82-3 ]
YieldReaction ConditionsOperation in experiment
86% 1-bromo-3-(trifluoromethyl)benzene (5.00 g, 22 mmol) was placed in a 250 ml reaction flask, followed by injecting and evacuating nitrogen gas three times. Next, dehydrated tetrahydrofuran (THF, 100 ml) was added into the reaction flask, followed by slowly adding 9.8 ml n-butyllithium in hexane solution (2.5M, 24 mmol) at -78 C. and stirring at the same temperature for 30 minutes. Thereafter, 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5.0 ml, 24 mmol) was added into the reaction flask to obtain a mixture, and the temperature of the mixture was raised to room temperature, followed by stirring at room temperature for 12 hours. Next, water was added to terminate the reaction followed by removing THF using a rotary evaporator. Then, dichloromethane and water were added into the mixture for extraction. The dichloromethane layer was collected and added with magnesium sulfate to remove water therein. After water was removed, the dichloromethane layer was filtrated and the filtrate was collected. Next, the dichloromethane layer was concentrated by means of reduced pressure distillation to obtain a colorless oily liquid (5.21 g, 19 mmol, 86% yield). The spectrum analysis for the colorless oily liquid is: 1H NMR (400 MHz, CDCl3, 298K), delta(ppm): 8.04 (s, 1H), 7.95 (d, JHH=7.6 Hz, 1H), 7.68 (d, JHH=7.6 Hz, 1H), 7.46 (t, JHH=7.6 Hz, 1H), 1.34 (s, 12H).
 

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