Structure of N-Boc-4-bromopiperidine
CAS No.: 180695-79-8
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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.
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Keywords: quantum dot ; nanoplatelet ; nickel ; cross-electrophile coupling ; C−C bond formation ; photochemistry
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Purchased from AmBeed: 83948-53-2 ; 180695-79-8 ; 166953-64-6 ; 131379-33-4 ; 364359-05-7
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| 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 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H302-H319 |
| Precautionary Statements: | P264-P270-P280-P301+P312-P305+P351+P338-P337+P313 |
| 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 |
29.54 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.96 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.43 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.4 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.15 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.71 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.33 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-2.81 |
| Solubility | 0.408 mg/ml ; 0.00155 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-2.69 |
| Solubility | 0.535 mg/ml ; 0.00203 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.13 |
| Solubility | 1.97 mg/ml ; 0.00745 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| 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) |
No |
| CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
| CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.19 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
0.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.46 |
* 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.

| Yield | Reaction Conditions | Operation 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 |
[ 176022-47-2 ]
[ 180695-79-8 ]
| Yield | Reaction Conditions | Operation 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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