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Structure of (S)-(-)-Phenylethanol
CAS No.: 1445-91-6
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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.
Synonyms: (S)-(-)-1-Phenylethanol; (S)-1-Phenylethanol
4.5
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Synthesis and Characterization of Enantioenriched Deuterated and Fluorinated Small Molecules
Mills, Mitchell ;
Abstract: The development of novel deuterated and fluorinated bioisosteres has significantly impacted the pharmaceutical and agricultural industry and created a growing demand for new synthetic methodology. Both deuterated and fluorinated small molecules exist at the forefront of drug discovery due to their unique ability to attenuate the pharmacokinetic properties of new and currently existing drugs. Selective, highthroughput methods for deuteration and fluorination are scarce in the literature, especially methods that introduce D or F atoms asymmetrically. Benzylic C−H bonds are oftentimes key sites for enzymatic manipulation in metabolic processes, alteration of C−H bonds to C−D or C−F bonds at the benzylic site of organic molecules affects the metabolic process, making this a key site for bioisosterism. Using state-of-the-art methods to synthesize chiral by virtue of deuterium small molecules requires significant synthetic overhead with limited methods for chiral analysis due to the similar nature of H and D. Asymmetric fluorination has been restricted to α,β-unsaturated carbonyl compounds that can transform into metal enolates, and only two literature examples of enantioselective fluorinations of aryl alkenes. Herein, enantioselective methods for both deuteration and fluorination are described. Regio- and enantioselective hydrodeuteration of the π-bond of aryl alkenes was successfully achieved using a chiral Cu−H catalyst with a protic D-source. Molecular rotational resonance (MRR) spectroscopy was utilized as a novel analytical method for determining %ee, absolute stereochemistry, and identifying isotopomers and isotopologues. This substrate scope includes various aromatic and heteroaromatic alkenes with excellent yields and high enantioselectivities. By substituting the protic D-source for Selectfluor, an electrophilic fluorinating reagent, enantioselective fluorination was also achieved. Optimization of the catalytic conditions will reveal the feasibility of achieving high enantioselectivities and yields. In this work, my contributions to both the deuteration and fluorination projects is described.
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Purchased from AmBeed: 1445-91-6
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CAS No. : | 1445-91-6 |
Formula : | C8H10O |
M.W : | 122.16 |
SMILES Code : | C[C@H](O)C1=CC=CC=C1 |
Synonyms : |
(S)-(-)-1-Phenylethanol; (S)-1-Phenylethanol
|
MDL No. : | MFCD00064264 |
InChI Key : | WAPNOHKVXSQRPX-ZETCQYMHSA-N |
Pubchem ID : | 443135 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H311-H315-H318 |
Precautionary Statements: | P501-P264-P280-P361+P364-P332+P313-P302+P352+P312-P305+P351+P338+P310-P405 |
Class: | 8(6.1) |
UN#: | 2922 |
Packing Group: | Ⅲ |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 37.38 |
TPSA ? Topological Polar Surface Area: Calculated from |
20.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.91 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.42 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.42 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.87 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.86 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.7 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.92 |
Solubility | 1.47 mg/ml ; 0.012 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.45 |
Solubility | 4.34 mg/ml ; 0.0355 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.21 |
Solubility | 0.752 mg/ml ; 0.00615 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) |
Yes |
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 |
-6.04 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 |
2.0 |
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 |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.0 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With caesium carbonate; In acetonitrile; for 24h;Inert atmosphere; Reflux; | General procedure: 6-Bromo-4-chlorothieno[2,3-d]pyrimidine(5a) (200 mg, 0.802 mmol) was mixed with 1-phenylethanol (2a) (118 mg, 0.962 mmol), Cs2CO3( 313 mg, 0.962 mmol) and acetonitrile (2 mL). The reaction was then stirredunder nitrogen atmosphere at reflux and followed by GC. The mixture was cooledto rt, diluted with EtOAc (40 mL), washed with sat. aq. KHCO3 (20mL), water (2×20 mL) and brine (30 mL). The combined organic fractions weredried over Na2SO4 and concentrated in vacuum. Crudeproduct was absorbed onto Celite 545 and purified by silica gel columnchromatography (n-pentane/EtOAc,6/1). This gave 245 mg (0.730 mmol, 91%) of 6a as an off-white solid. |
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