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Chemical Structure| 180695-79-8 Chemical Structure| 180695-79-8

Structure of N-Boc-4-bromopiperidine
CAS No.: 180695-79-8

Chemical Structure| 180695-79-8

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Product Citations

Product Citations

Julianna M. Mouat ; Jonas K. Widness ; Daniel G. Enny ; Mahilet T. Meidenbauer ; Farwa Awan ; Todd D. Krauss , et al.

Abstract: Semiconductor quantum dots (QDs) offer many advantages as photocatalysts for synthetic photoredox catalysis, but no reports have explored the use of QDs with nickel catalysts for C–C bond formation. We show here that 5.7 nm CdS QDs are robust photocatalysts for photoredox-promoted cross-electrophile coupling (turnover number (TON) up to 40,000). These conditions can be utilized on a small scale (96-well plate) or adapted to flow. NMR studies show that triethanolamine (TEOA)-capped QDs are the active catalyst and that TEOA can displace native phosphonate and carboxylate ligands, demonstrating the importance of the QD surface chemistry.

Keywords: quantum dot ; nanoplatelet ; nickel ; cross-electrophile coupling ; C−C bond formation ; photochemistry

Purchased from AmBeed: ; ; ; ;

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Product Details of [ 180695-79-8 ]

CAS No. :180695-79-8
Formula : C10H18BrNO2
M.W : 264.16
SMILES Code : BrC1CCN(C(OC(C)(C)C)=O)CC1
MDL No. :MFCD04115039
InChI Key :KZBWIYHDNQHMET-UHFFFAOYSA-N
Pubchem ID :15541517

Safety of [ 180695-79-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H319
Precautionary Statements:P264-P270-P280-P301+P312-P305+P351+P338-P337+P313

Computational Chemistry of [ 180695-79-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 0
Fraction Csp3 0.9
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 64.46
TPSA ?

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

29.54 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.96
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

2.43
Log Po/w (WLOGP)?

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

2.4
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.

2.15
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

1.71
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.33

Water Solubility

Log S (ESOL):?

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

-2.81
Solubility 0.408 mg/ml ; 0.00155 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.

-2.69
Solubility 0.535 mg/ml ; 0.00203 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

-2.13
Solubility 1.97 mg/ml ; 0.00745 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

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

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.

-6.19 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<0.0
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)

2.46

Application In Synthesis of [ 180695-79-8 ]

* 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 [ 180695-79-8 ]

[ 180695-79-8 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 24424-99-5 ]
  • [ 54288-70-9 ]
  • [ 180695-79-8 ]
YieldReaction ConditionsOperation in experiment
100% Step 1: Synthesis of 4-Bromo-piperidine-1-carboxylic acid tert-butyl ester To a suspension of 5 g (0.02 mol) of <strong>[54288-70-9]4-bromopiperidine hydrobromide</strong> salt in DCM (35 mL) are added 7.09 mL (0.04 mol) of N,N-diisopropylethyl amine dropwise at 0° C. The reaction mixture is stirred for 30 min, then a solution of 6.67 g (0.31 mol) of di-tert-butyl dicarbonate in DCM (35 mL) is added dropwise to the reaction mixture. The reaction mixture is stirred for 18 h at room temperature, then washed with 1M aqueous HCl solution (2*30 mL) and brine (30 mL). The organic layer is dried over Na2SO4, filtered and the filtrate is concentrated under reduced pressure to afford 6.9 g of 4-bromo-piperidine-l-carboxylic acid tert-butyl ester as a yellow oil. Yield quantitative; 1H NMR (250 MHz, CHLOROFORM-d) delta ppm 1.46 (9H, s), 1.79-2.00 (2H, m), 2.00-2.16 (2H, m), 3.31 (2H, ddd, J=13.67, 7.73, 3.73 Hz), 3.68 (2H, ddd, J=13.55, 6.85, 3.65 Hz), 4.34 (1H, tt, J=7.69, 3.81 Hz)
100% With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; To a suspension of 5 g (0.02 mol) of Compound 29 salt in DCM (35 mL) are added 7.09 mL (0.04 mol) of N,N-diisopropylethyl amine dropwise at 0° C. The reaction mixture is stirred for 30 min, then a solution of 6.67 g (0.31 mol) of di-tert-butyl dicarbonate in DCM (35 mL) is added dropwise to the reaction mixture. The reaction mixture is stirred for 18 h at room temperature, washed with 1M aqueous HCl solution (2.x.30 mL) and brine (30 mL). The organic layer is dried over Na2SO4, filtered and the filtrate is concentrated under reduced pressure to afford 6.9 g of Compound 30 as a yellow oil. Yield quantitative; 1H NMR (250 MHz, CHLOROFORM-d) delta ppm 1.46 (9H, s), 1.79-2.00 (2H, m), 2.00-2.16 (2H, m), 3.31 (2H, ddd, J=13.67, 7.73, 3.73 Hz), 3.68 (2H, ddd, J=13.55, 6.85, 3.65 Hz), 4.34 (1H, tt, J=7.69, 3.81 Hz).
98% With triethylamine; In tetrahydrofuran; at 20℃; for 48h; Triethylamine (2.3 mL, 16.3 mmol) and di-tert-butyl dicarbonate (1.9 g, 8.6 mmol) were added to astirred suspension of <strong>[54288-70-9]4-bromopiperidine hydrobromide</strong> (2.0 g, 8.2 mmol) in THF (40 mL). Thereaction mixture was stirred for 48 h at rt. The suspension was filtered and the filter was washedwith THF. The combined filtrate was evaporated in vacuo. Purification by flash chromatography(petroleum ether 40?60 °C/EtOAc, 95:5 v/v) afforded 19 (2.11 g, 98percent) as colourless oil
  • 2
  • [ 163622-50-2 ]
  • [ 180695-79-8 ]
  • [ 330793-48-1 ]
  • 3
  • [ 176022-47-2 ]
  • [ 180695-79-8 ]
  • (S)-N-tert-butoxycarbonyl-4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% The tetrahydrofuran in Example 1 was replaced by the same amount of N, N-dimethylformamide, and the other procedures were the same as in Example 1,Rate 88%. (S) - (4-chlorophenyl) (2-pyridyl) -methanol 21.9 g (0.1 mol) of the formula (II)Was dissolved in 160 mL of tetrahydrofuran,41 g (0.1 mol) of sodium hydride in a mass fraction of 60% was added portionwise with stirring,Stirring for 2 hours to no bubbles,The reaction was allowed to cool under ice-coolingA solution of 26.4 g (0.1 mol) of N-t-butoxycarbonyl-4-bromopiperidine was added dropwise,After completion of the dropwise addition, the reaction was gradually warmed to room temperature with stirring for 5 hours,The reaction solution was added to 200 mL of saturated ammonium chloride solution,Stirred for 30 minutes,The reaction solution was extracted twice with 300 mL of ethyl acetate,The organic phases were combined,Dried over anhydrous sodium sulfate for 2 hours,filter,The mother liquor was evaporated to dryness to give 34.3 g of product,The product was directly subjected to the next reaction without purification,Yield 85%.
 

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Technical Information

Categories

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