Home Cart Sign in  
Chemical Structure| 76041-73-1 Chemical Structure| 76041-73-1

Structure of 76041-73-1

Chemical Structure| 76041-73-1

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

,{[proInfo.pro_purity]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size Price VIP Price

US Stock

Global Stock

In Stock
{[ item.pr_size ]} Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

  • {[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

  • 1-2 Day Shipping
  • High Quality
  • Technical Support
Product Citations

Alternative Products

Product Details of [ 76041-73-1 ]

CAS No. :76041-73-1
Formula : C6H3BrF3NO
M.W : 241.99
SMILES Code : OC1=NC=C(C(F)(F)F)C=C1Br
MDL No. :MFCD02691223
InChI Key :UWHKLLYQUQPOQK-UHFFFAOYSA-N
Pubchem ID :13491775

Safety of [ 76041-73-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H317-H319
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 76041-73-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 1
Num. H-bond acceptors 5.0
Num. H-bond donors 1.0
Molar Refractivity 38.96
TPSA ?

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

33.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.83
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

2.41
Log Po/w (WLOGP)?

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

3.72
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.

2.08
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

2.6
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.53

Water Solubility

Log S (ESOL):?

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

-3.16
Solubility 0.166 mg/ml ; 0.000688 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-2.75
Solubility 0.433 mg/ml ; 0.00179 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

-3.19
Solubility 0.154 mg/ml ; 0.000638 mol/l
Class?

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

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

No
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

Yes
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

No
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.

-6.07 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

0.0 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)

1.86

Application In Synthesis of [ 76041-73-1 ]

* 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 [ 76041-73-1 ]

[ 76041-73-1 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 33252-63-0 ]
  • [ 76041-73-1 ]
YieldReaction ConditionsOperation in experiment
99.8% To a solution of 5-(trifluoromethyl)pyridin-2-ol (10.52 g, 62 mmol) and sodium acetate (5.29 g, 64 mmol) in glacial acetic acid (38 mL) was added bromine (3.36 mL, 65 mmol) at room temperature. The white cloudy solution slowly turned into a clear brown solution, which was heated at 80 C. for 2.5 h. The mixture was allowed to cool to room temperature and then evaporated under reduced pressure. The residue was neutralized with saturated NaHCO3 solution to pH=8. The resulting solution was extracted with EtOAc three times. The combined extracts were dried over MgSO4, filtered, and evaporated in vacuo to yield 15.1 g (99.8%) of the crude product (15.1 g, 98.8%) as a white solid. LC-MS calculated for C6H3BrF3NO: (M+H)+241.9; found 241.9/243.9. Step A-2
98% With bromine; sodium acetate; In acetic acid; at 80℃; for 2.5h; To a solution of 5-trifluoromethyl-2-pyridinal (51 g, 310 mmol) and sodium acetate (26. 2G, 319 mmol) in glacial acetic acid (200 mL) was added bromine (16.7 ML, 325 mmol) and the resulting mixture was heated at 80 C for 2.5 h. The reaction was allow to cool to room temperature and then was evaporated under reduced pressure. The residue was neutralized with saturated NaHC03 solution and extracted with ethyl acetate (3 x 200 mL). The organics were combined, dried over MGS04, filtered, and evaporated in vacuo to yield 74.45 g (98%) of the crude product. 1H NMR (400 MHz, CDC13) 8 8.04 (d, J=2.6 Hz, 1H), 7.89 (m, 1H).
98.7% With bromine; sodium acetate; In acetic acid; at 80℃; for 2.5h; To a solution of 5-TRIFLUOROMETHYL-2-PYRIDINOL (51. 0 g, 307 mmol) and sodium acetate (26.2 g, 319 mmol) in glacial acetic acid (200 mL) was added bromine (16.7 mL, 325 mmol) and the resulting mixture was heated at 80 C for 2.5 hours. The reaction was allow to cool to room temperature and then was evaporated under reduced pressure. The residue was neutralized with saturated NAHC03 solution and extracted with ethyl acetate (3 x 200 mL). The organic layers were combined, dried over MgS04, filtered, and evaporated in vacuo to yield 74.45 g (98.7%) of the crude PRODUCT. H NMR (400 MHz, CD) 5 8.04 (d, J=2.6 Hz, 1H), 7.89 (m, 1H).
98.7% INTERMEDIATE 2; Step A; To a solution of 5-trifluoromethyl-2-pyridinol (51.0 g, 307 mmol) and sodium acetate (26.2 g, 319 mmol) in glacial acetic acid (200 mL) was added bromine (16.7 mL, 325 mmol) and the resulting mixture was heated at 80 C. for 2.5 hours. The reaction was allow to cool to room temperature and then was evaporated under reduced pressure. The residue was neutralized with saturated NaHCO3 solution and extracted with ethyl acetate (3×200 mL). The organic layers were combined, dried over MgSO4, filtered, and evaporated in vacuo to yield 74.45 g (98.7%) of the crude product. 1H NMR (400 MHz, CDCl3) delta 8.04 (d, J=2.6 Hz, 1H), 7.89 (m, 1H).
98% With bromine; sodium acetate; In acetic acid; at 80℃; for 2.5h; To a solution of 5-trifluoromethyl-2-pyridinal (51 g, 310 mmol) and sodium acetate (26.2 g, 319 mmol) in glacial acetic acid (200 mL) was added bromine (16.7 mL, 325 mmol) and the resulting mixture was heated at 80 C. for 2.5 h. The reaction was allowed to cool to room temperature and then was evaporated under reduced pressure. The residue was neutralized with saturated NaHCO3 solution and extracted with ethyl acetate (3×200 mL). The organics were combined, dried over MgSO4, filtered, and evaporated in vacuo to yield 74.45 g (98%) of the crude product. 1H NMR (400 MHz, CDCl3) delta 8.04 (d, J=2.6 Hz, 1H), 7.89 (m, 1H).
98.7% With bromine; sodium acetate; In acetic acid; at 80℃; for 2.5h; To a solution of 5-trifluoromethyl-2-pyridinol (51.0 g, 307 mmol) and sodium acetate (26.2 g, 319 mmol) in glacial acetic acid (200 mL) was added bromine (16.7 mL, 325 mmol) and the resulting mixture was heated at 80 C. for 2.5 hours. The reaction was allow to cool to room temperature and then was evaporated under reduced pressure. The residue was neutralized with saturated NaHCO3 solution and extracted with ethyl acetate (3×200 mL). The organic layers were combined, dried over MgSO4, filtered, and evaporated in vacuo to yield 74.45 g (98.7%) of the crude product. 1H NMR (400 MHz, CDCl3) delta 8.04 (d, J=2.6 Hz, 1H), 7.89 (m, 1H).
95% With bromine; sodium acetate; In acetic acid; at 80℃; for 2h; To a solution of 5-TRIFLUOROMETHYL-2-PYRIDINOL (21.37 g, 131 mmol), and sodium acetate (11.23 g , 107 mmol) in glacial acetic acid was added bromine (6.94 ml, 135 mmol), and the resulting mixture stirred at 80 C for 2 hours. The cooled reaction mixture was evaporated and the residue basified by the addition of saturated NAHC03 (500 ml), and extracted with ethyl acetate (3 x 300 ml); the combined ethyl acetate layers were dried over MGS04, filtered and evaporated in vacuo to give the product (30.21 g, 95%) ; IH NMR 500MHZ (CDC13) 8 = 8.00 (1H, d, J = 2.29 Hz), 8.16 (LH, d, J=2. 29HZ).
85% With N-Bromosuccinimide; In N,N-dimethyl-formamide; for 2h; lambda/-bromosuccinimide (NBS, 39.0Og, 0.22 mol) is added portionwise to a solution of 5-(trifluoromethyl)pyridin-2-ol (30.0Og, 0.18 mol) in DMF (180 ml_), and the resulting mixture is stirred for 2 hours. The mixture is poured into water (1200 mL) and the precipitate was collected by filtration. The crystal is dried in vacuo to give the product as a white solid (1st crystal : 28.1Og). The filtrate is extracted with EtOAc, and the organic layer is concentrated.The residue is poured into water and the precipitate is collected by filtration. The crystal is dried in vacuo to give 3-bromo-5-(trifluoromethyl)pyridin-2-ol (2nd crystal : 9.65 g, total:37.75g, 85 % yield) as a yellow solid.1H-NMR (400MHz, CDCI3), delta (ppm): 7.86 (d, 1H), 8.02 (d, 1H), 13.17 (br, 1H).
With N-Bromosuccinimide; In N,N-dimethyl-formamide; for 2h; V-bromosuccinimide (NBS, 39.0Og, 0.22 mol) is added portionwise to a solution of 5- {trifluoromethyl)pyridin-2-ol (30.0Og, 0.18 mol) in DMF (180 ml_), and the resulting mixture is stirred for 2 hours. The mixture is poured into water (1200 ml.) and the precipitate is collected by filtration. The crystal is dried in vacuo to give the product as a white solid (1st crystal : 28.1Og). The filtrate is extracted with EtOAc, and the organic layer is concentrated. The residue is poured into water and the precipitate is collected by filtration. The crystal is dried in vacuo to give 3-bromo-5-(trifluoromethyl)pyridin-2-ol as a yellow solid. 1H-NMR (400MHz, CDCI3), delta (ppm): 7.86 (d, 1 H), 8.02 (d, 1 H), 13.17 (br, 1 H).
With N-Bromosuccinimide; In N,N-dimethyl-formamide; for 2h; lambda/-bromosuccinimide (NBS, 39.0Og, 0.22 mol) is added portionwise to a solution of 5- (trifluoromethyl)pyridin-2-ol (30.0Og, 0.18 mol) in DMF (180 mL), and the resulting mixture is stirred for 2 hours. The mixture is poured into water (1200 mL) and the precipitate is collected by filtration. The crystal is dried in vacuo to give the product as a white solid (1st crystal : 28.1Og). The filtrate is extracted with EtOAc, and the organic layer is concentrated. The residue is poured into water and the precipitate is collected by filtration. The crystal is dried in vacuo to give 3-bromo-5-(trifluoromethyl)pyridin-2-ol as a yellow solid. <n="45"/>Case 505091H-NMR (400MHz, CDCI3), delta (ppm): 7.86 (d, 1 H), 8.02 (d, 1H), 13.17 (br, 1 H).
With bromine; sodium acetate; In acetic acid; at 80℃; for 2.5h; INTERMEDIATE 4 To a solution of 5-trifluoromethyl-2-pyridinal (51 g, 310 mmol) and sodium acetate (26.2g, 319 mmol) in glacial acetic acid (200 mL) was added bromine (16.7 mL, 325 mmol) and the resulting mixture was heated at 80 C for 2.5 h. The reaction was allow to cool to room temperature and then was evaporated under reduced pressure. The residue was neutralized with saturated NaHC03 solution and extracted with ethyl acetate (3 x 200 mL). The organics were combined, dried over MgS04, filtered, and evaporated in vacuo to yield 74.45 g (98%) of the crude product.

  • 2
  • [ 76041-73-1 ]
  • [ 68-12-2 ]
  • [ 129904-48-9 ]
YieldReaction ConditionsOperation in experiment
100% <strong>[76041-73-1]3-Bromo-5-(trifluoromethyl)pyridin-2-ol</strong> (8.20 g, 31.2 mmol) was added in small portions to a suspension of sodium hydride (0.8575 g, 33.94 mmol) in anhydrous THF (76 mL) at room temperature. After complete addition, the reaction mixture was cooled to -78 C. and treated with a 1.7 M solution of tert-butyllithium in pentane (40.0 mL) which was added dropwise via a syringe over a period of 15 min. After stirring for 5 min, anhydrous DMF (8.16 mL, 105 mmol) was added slowly while maintaining the temperature below -50 C. The reaction mixture was then stirred overnight allowing it to warm to room temperature. The resulting light brown mixture was quenched by addition of a saturated NH4Cl solution. The pH of the solution was adjusted to 9-10 by addition of aqueous NaHCO3. The resulting solution was extracted with EtOAc four times. The combined extracts were dried (MgSO4), filtered and concentrated to provide a brown solid crude product (7.33 g, >100% crude yield). MS calculated for C7H4F3NO2 (M+H)+192; found 192.1.
74% With tert.-butyl lithium; sodium hydride; In tetrahydrofuran; at -78 - 20℃; for 10h; Under nitrogen, the substituted pyridine described in Step A (48.8g, 202 mmol) was added in small portions to a suspension OF NAH (8. 9 g, 220 mmol) in anhydrous tetrahydrofuran (500 mL). After complete addition of the intermediate, the reaction mixture was cooled to-78 C and treated with tert-butyllithium (260 ML, 444 mmol) added dropwise via syringe. After stirring for 5 min, N, N- dimethylformamide (50 ML, 707 mmol) was added slowly to maintain the temperature BELOW-50 C. The resulting mixture was then stirred for 10 h allowing it to warm to room temperature. The mixture was quenched with 2 N HC1 and then diluted with ethyl acetate (1000 mL). The organic layer was separated, washed with brine, dried over MGS04, and evaporated in vacuo. The desired product was precipitated out of ethyl acetate and hexanes and filtered to yield a light brown solid (28.55 g, 74%). 1H NMR (500 MHz, CD30D) 8 10.13 (s, 1H), 8.21 (s, 2H).
74% Step B; Under nitrogen, the substituted pyridine described in Step A, Intermediate 7 (48.8g, 202 mmol) was added in small portions to a suspension of NaH (8.9 g, 220 mmol) in anhydrous tetrahydrofuran (500 mL). After complete addition of the intermediate, the reaction mixture was cooled to-78 C and treated with tert-butyllithium (260 mL, 444 mmol) added dropwise via syringe. After stirring for 5 min, N, N- dimethylformamide (50 mL, 707 mmol) was added slowly to maintain the temperature below-50 C. The resulting mixture was then stirred for 10 h allowing it to warm to room temperature. The mixture was quenched with 2 N HCl and then diluted with ethyl acetate (1000 mL). The organic layer was separated, washed with brine, dried over MgS04, and evaporated in vacuo. The desired product was precipitated out of ethyl acetate and hexanes and filtered to yield a light brown solid (28.55 g, 74%). 1H NMR (500 MHz, CD30D) 8 10.13 (s, 1H), 8.21 (s, 2H).
74% Step B; Under nitrogen, the substituted pyridine described in Step A, Intermediate 8 (48.8g, 202 mmol) was added in small portions to a suspension of NaH (8. 9 g, 220 mmol) in anhydrous tetrahydrofuran (500 mL). After complete addition of the intermediate, the reaction mixture was cooled to-78 C and treated with tert-butyllithium (260 mL, 444 mmol) added dropwise via syringe. After stirring for 5 min, N, N-dimethylformamide (50 mL, 707 mmol) was added slowly to maintain the temperature below-50 C. The resulting mixture was then stirred for 10 h allowing it to warm to room temperature. The mixture was quenched with 2 N HC1 and then diluted with ethyl acetate (1000 mL). The organic layer was separated, washed with brine, dried over MgS04, and evaporated i71 vacuo. The desired product was precipitated out of ethyl acetate and hexanes and filtered to yield a light brown solid (28. 55 g, 74%).
73.8% Under nitrogen, the substituted pyridine, described in Step A (48.8 g, 202 mmol) was added by small portions to a suspension of NaH (8.9 g, 220 mmol) in anhydrous THF (500 mL). After complete addition of the intermediate, the reaction mixture was cooled to -78 C. and treated with tert-butyllithium (260 mL, 444 mmol) added dropwise via syringe. After stirring for 5 minutes, DMF (50 mL, 707 mmol) was added slowly to maintain the temperature below -50 C. The resulting mixture was then stirred for 10 hours allowing to warm to room temperature. The mixture was quenched with 2N HCl and then diluted with ethyl acetate (1000 mL). The organic layer was separated, washed with brine, dried over MgSO4, and evaporated in vacuo. The desired product was precipitated out of ethyl acetate and hexane and filtered to yield a light brown solid (28.55 g, 73.8%). 1H NMR (500 MHz, CD3OD) delta 10.13 (s, 1H), 8.21 (s, 2H).

  • 3
  • [ 76041-73-1 ]
  • [ 129904-48-9 ]
YieldReaction ConditionsOperation in experiment
74% Under nitrogen, the substituted pyridine described in Step A, Intermediate 11 (48.8 g, 202 mmol) was added in small portions to a suspension of NaH (8.9 g, 220 mmol) in anhydrous tetrahydrofuran (500 mL). After complete addition of the intermediate, the reaction mixture was cooled to -78 C. and treated with tert-butyllithium (260 mL, 444 mmol) added dropwise via syringe. After stirring for 5 min, N,N-dimethylformamide (50 mL, 707 mmol) was added slowly to maintain the temperature below -50 C. The resulting mixture was then stirred for 10 h allowing it to warm to room temperature. The mixture was quenched with 2 N HCl and then diluted with ethyl acetate (1000 mL). The organic layer was separated, washed with brine, dried over MgSO4, and evaporated in vacuo. The desired product was precipitated out of ethyl acetate and hexanes and filtered to yield a light brown solid (28.55 g, 74%). 1H NMR (500 MHz, CD3OD) delta 10.13 (s, 1H), 8.21 (s, 2H).
73.8% Under nitrogen, the substituted pyridine, described in Step A (48.8g, 202 mmol) was added by small portions to a suspension of NaH (8.9 g, 220 mmol) in anhydrous THF (500 ML). After complete addition of the intermediate, the reaction mixture was cooled to-78 C and treated with tert-butyllithium (260 mL, 444 mmol) added dropwise via syringe. After stirring for 5 minutes, DMF (50 mL, 707 mmol) was added slowly to maintain the temperature below- 50 C. The resulting mixture was then stirred for 10 hours allowing to warm to room temperature. The mixture was quenched with 2N HCI and then diluted with ethyl acetate (1000 mL). The organic layer was separated, washed with brine, dried over MGS04, and evaporated in vacuo. The desired product was precipitated out of ethyl acetate and hexane and filtered to yield a light brown solid (28.55 g, 73. 8%). H NMR (500 MHz, CD30D) 8 10.13 (s, 1H), 8.21 (s, 2H).
  • 4
  • [ 33252-63-0 ]
  • [ 76041-73-1 ]
YieldReaction ConditionsOperation in experiment
98% With bromine; sodium acetate; acetic acid; at 80℃; for 2.5h; INTERMEDIATE 7 Step A; To a solution of 5-trifluoromethyl-2-pyridinal (51 g, 310 mmol) and sodium acetate (26.2g, 319 mmol) in glacial acetic acid (200 mL) was added bromine (16.7 mL, 325 mmol) and the resulting mixture was heated at 80 C for 2.5 h. The reaction was allow to cool to room temperature and then was evaporated under reduced pressure. The residue was neutralized with saturated NaHC03 solution and extracted with ethyl acetate (3 x 200 mL). The organics were combined, dried over MgS04, filtered, and evaporated in vacuo to yield 74.45 g (98%) of the crude product. 1H NMR (400 MHz, CDC13) 8 8.04 (d, J=2.6 Hz, 1H), 7.89 (m, 1H).
98% With bromine; sodium acetate; acetic acid; at 80℃; for 2.5h; INTERMEDIATE 7; Step A; To a solution of 5-trifluoromethyl-2-pyridinal (51 g, 310 mmol) and sodium acetate (26.2g, 319 mmol) in glacial acetic acid (200 mL) was added bromine (16.7 mL, 325 mmol) and the resulting mixture was heated at 80 C for 2.5 h. The reaction was allow to cool to room temperature and then was evaporated under reduced pressure. The residue was neutralized with saturated NaHC03 solution and extracted with ethyl acetate (3 x 200 mL). The organics were combined, dried over MgS04, filtered, and evaporated ilz vacuo to yield 74.45 g (98%) of the crude product.
  • 5
  • [ 76041-73-1 ]
  • [ 71701-92-3 ]
YieldReaction ConditionsOperation in experiment
79% A mixture of <strong>[76041-73-1]3-bromo-5-(trifluoromethyl)pyridin-2-ol</strong> (37.75g, 0.16 mol) and phosphorus(lll) oxychloride (POCI3; 75 mL) is stirred at 1000C for 5 hours. After cooling to room temperature, the mixture is poured into ice-water, and extracted with CH2CI2 twice. The combined organic layer is washed with NaHCO3 aq., brine, dried over MgSO4, filtered and concentrated in vacuo. The crude mixture is purified by flash column chromatography to give 3-bromo-2-chloro-5-trifluoromethylpyridine (31.90 g, 79 % yield) as a white solid. 1H-NMR (400MHz, CDCI3), delta (ppm): 8.17 (m, 1H), 8.62 (d, 1 H).
A mixture of <strong>[76041-73-1]3-bromo-5-(trifluoromethyl)pyridin-2-ol</strong> (37.75g, 0.16 mol) and phosphorus(lll) oxychloride (POCI3; 75 mL) is stirred at 1000C for 5 hours. After cooling to room temperature, the mixture is poured into ice-water, and extracted with CH2CI2 twice. The combined organic layer is washed with NaHCO3 aq., brine, dried over MgSO4, filtered and concentrated in vacuo. The crude mixture is purified by flash column chromatography to give 3-bromo-2-chloro-5-trifluoromethylpyridine as a white solid. 1H-NMR (400MHz, CDCI3), delta (ppm): 8.17 (m, 1H), 8.62 (d, 1 H).
A mixture of <strong>[76041-73-1]3-bromo-5-(trifluoromethyl)pyridin-2-ol</strong> (37.75g, 0.16 mol) and phosphorus(lll) oxychloride (POCI3; 75 mL) is stirred at 1000C for 5 hours. After cooling to room temperature, the mixture is poured into ice-water, and extracted with CH2CI2 twice. The combined organic layer is washed with NaHCO3 aq., brine, dried over MgSO4, filtered and concentrated in vacuo. The crude mixture is purified by flash column chromatography to give 3-bromo-2-chloro-5-trifluoromethylpyridine as a white solid. 1H-NMR (400MHz, CDCI3), delta (ppm): 8.17 (m, 1 H), 8.62 (d, 1 H).
  • 6
  • [ 76041-73-1 ]
  • [ 439948-91-1 ]
  • C14H18BrF3N2O3 [ No CAS ]
  • 7
  • [ 76041-73-1 ]
  • N-(octaaminoquinoline)but-3-enamide [ No CAS ]
  • 4-(3-bromo-2-oxo-5-(trifluoromethyl)pyridin-1(2H)-yl)-N-(quinolin-8-yl)butanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With palladium diacetate; acetic acid; In acetonitrile; at 120℃; for 4h;Sealed tube; General procedure: Unless otherwise stated, the procedure was as follows. To a 1-dram (4 mL) vial equipped with a magnetic stir bar were added Pd(OAc)2 (4.4 mg, 0.02 mmol), alkene (0.2 mmol), acetic acid (6.0 mg, 0.1 mmol), nucleophile (0.3 mmol), and MeCN (0.1 mL). The vial was sealed with an unpunctured TFE septum-covered screw cap, and placed in a heating block that was pre-heated to 120 C. After the designated reaction time, the dark black reaction was purified either by flash column chromatography only or by flash column chromatography followed by an aqueous workup to produce the desired product.
 

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 76041-73-1 ]

Fluorinated Building Blocks

Chemical Structure| 1211521-34-4

A930880 [1211521-34-4]

3-Bromo-2-methoxy-4-(trifluoromethyl)pyridine

Similarity: 0.84

Chemical Structure| 1227494-05-4

A139045 [1227494-05-4]

4-Bromo-5-(trifluoromethyl)pyridin-2-ol

Similarity: 0.83

Chemical Structure| 436799-33-6

A230656 [436799-33-6]

3-Bromo-5-(trifluoromethyl)pyridine

Similarity: 0.81

Chemical Structure| 33252-63-0

A157588 [33252-63-0]

5-(Trifluoromethyl)pyridin-2-ol

Similarity: 0.79

Chemical Structure| 1227563-37-2

A136183 [1227563-37-2]

(3-Bromo-5-(trifluoromethyl)pyridin-2-yl)methanol

Similarity: 0.76

Bromides

Chemical Structure| 1211521-34-4

A930880 [1211521-34-4]

3-Bromo-2-methoxy-4-(trifluoromethyl)pyridine

Similarity: 0.84

Chemical Structure| 1227494-05-4

A139045 [1227494-05-4]

4-Bromo-5-(trifluoromethyl)pyridin-2-ol

Similarity: 0.83

Chemical Structure| 17282-02-9

A197426 [17282-02-9]

3-Bromo-5-methylpyridin-2-ol

Similarity: 0.81

Chemical Structure| 436799-33-6

A230656 [436799-33-6]

3-Bromo-5-(trifluoromethyl)pyridine

Similarity: 0.81

Chemical Structure| 717843-56-6

A112777 [717843-56-6]

3-Bromo-2-methoxy-5-methylpyridine

Similarity: 0.79

Alcohols

Chemical Structure| 1227494-05-4

A139045 [1227494-05-4]

4-Bromo-5-(trifluoromethyl)pyridin-2-ol

Similarity: 0.83

Chemical Structure| 17282-02-9

A197426 [17282-02-9]

3-Bromo-5-methylpyridin-2-ol

Similarity: 0.81

Chemical Structure| 33252-63-0

A157588 [33252-63-0]

5-(Trifluoromethyl)pyridin-2-ol

Similarity: 0.79

Chemical Structure| 1227563-37-2

A136183 [1227563-37-2]

(3-Bromo-5-(trifluoromethyl)pyridin-2-yl)methanol

Similarity: 0.76

Chemical Structure| 18368-59-7

A185636 [18368-59-7]

3-Bromo-4-methylpyridin-2-ol

Similarity: 0.74

Trifluoromethyls

Chemical Structure| 1211521-34-4

A930880 [1211521-34-4]

3-Bromo-2-methoxy-4-(trifluoromethyl)pyridine

Similarity: 0.84

Chemical Structure| 1227494-05-4

A139045 [1227494-05-4]

4-Bromo-5-(trifluoromethyl)pyridin-2-ol

Similarity: 0.83

Chemical Structure| 436799-33-6

A230656 [436799-33-6]

3-Bromo-5-(trifluoromethyl)pyridine

Similarity: 0.81

Chemical Structure| 33252-63-0

A157588 [33252-63-0]

5-(Trifluoromethyl)pyridin-2-ol

Similarity: 0.79

Chemical Structure| 1227563-37-2

A136183 [1227563-37-2]

(3-Bromo-5-(trifluoromethyl)pyridin-2-yl)methanol

Similarity: 0.76

Related Parent Nucleus of
[ 76041-73-1 ]

Pyridines

Chemical Structure| 1211521-34-4

A930880 [1211521-34-4]

3-Bromo-2-methoxy-4-(trifluoromethyl)pyridine

Similarity: 0.84

Chemical Structure| 1227494-05-4

A139045 [1227494-05-4]

4-Bromo-5-(trifluoromethyl)pyridin-2-ol

Similarity: 0.83

Chemical Structure| 17282-02-9

A197426 [17282-02-9]

3-Bromo-5-methylpyridin-2-ol

Similarity: 0.81

Chemical Structure| 436799-33-6

A230656 [436799-33-6]

3-Bromo-5-(trifluoromethyl)pyridine

Similarity: 0.81

Chemical Structure| 33252-63-0

A157588 [33252-63-0]

5-(Trifluoromethyl)pyridin-2-ol

Similarity: 0.79