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Chemical Structure| 5355-17-9 Chemical Structure| 5355-17-9

Structure of 5355-17-9

Chemical Structure| 5355-17-9

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Product Details of [ 5355-17-9 ]

CAS No. :5355-17-9
Formula : C8H10O2
M.W : 138.16
SMILES Code : OC1=CC=C(COC)C=C1
English Name :4-(Methoxymethyl)phenol
MDL No. :MFCD00020186
InChI Key :AHXXIALEMINDAW-UHFFFAOYSA-N
Pubchem ID :79310

Safety of [ 5355-17-9 ]

Computational Chemistry of [ 5355-17-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 39.32
TPSA ?

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

29.46 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.62
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

1.16
Log Po/w (WLOGP)?

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

1.39
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.

1.21
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

1.67
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.41

Water Solubility

Log S (ESOL):?

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

-1.74
Solubility 2.52 mg/ml ; 0.0182 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.37
Solubility 5.85 mg/ml ; 0.0423 mol/l
Class?

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

Very 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

-2.33
Solubility 0.654 mg/ml ; 0.00473 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.

-6.32 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

1.0
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)

1.0

Application In Synthesis of [ 5355-17-9 ]

* 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 [ 5355-17-9 ]

[ 5355-17-9 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 67-56-1 ]
  • [ 623-05-2 ]
  • [ 5355-17-9 ]
YieldReaction ConditionsOperation in experiment
91% at 20℃; for 2h;
91% With ammonium cerium(IV) nitrate at 20℃; for 2h;
85% With ytterbium(III) triflate In acetonitrile at 80℃; for 5h;
80% With hydrogenchloride; nitromethane In water at 30℃; for 5h; Inert atmosphere; 1 Example 1 4-methoxymethylphenol Into a 100 mL three-necked flask equipped with a thermometer, a three-way cock, and a stirring bar, under a nitrogen stream, 3.96 g (0.03 mol) of 4-hydroxybenzyl alcohol (manufactured by Tokyo Chemical Industry Co., Ltd.), 21 g of methanol (manufactured by Nacalai Tesque, Inc.), two drops of nitromethane (manufactured by Nacalai Tesque, Inc.) were added. While stirring at room temperature, 0.2 g of hydrochloric acid (manufactured by Nacalai Tesque, Inc.) was added dropwise, followed by stirring at 30 ° C. for 5 hours.The area percentage of HPLC at the end of the reaction was 95%. 0.28 g of pyridine (manufactured by Nacalai Tesque, Inc.) and 8 g of toluene (manufactured by Nacalai Tesque, Inc.) were added and neutralized, methanol was concentrated under reduced pressure, 31 g of toluene and 6 g of water were added to extract And the organic layer was washed with 5 g of water. The obtained organic layer was concentrated, cooled to 10 ° C. or less, and the precipitated crystals were filtered and dried to obtain 3.53 g (yield: 80%) of colorless 4-methoxymethylphenol. The HPLC purity was 99% (excluding solvent toluene).
66% With toluene-4-sulfonic acid for 6h; Ambient temperature;
at 150℃;
With hydrogenchloride Heating;
68.7 g With hydrogenchloride In water for 1h; Ambient temperature;
With hydrogenchloride
With sodium hydroxide for 4h; Heating;

  • 2
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
  • [ 5355-17-9 ]
YieldReaction ConditionsOperation in experiment
In methanol
  • 3
  • [ 67-56-1 ]
  • [ 39720-27-9 ]
  • [ 5355-17-9 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid In methanol for 48h; Ambient temperature;
  • 4
  • [ CAS Unavailable ]
  • [ 487-89-8 ]
  • [ 5355-17-9 ]
YieldReaction ConditionsOperation in experiment
With oxygen In methanol Irradiation; photozensitizer: eosin;
With oxygen In methanol Irradiation; photozensitizer;
  • 5
  • [ 67-56-1 ]
  • [ 2937-64-6 ]
  • [ 5355-17-9 ]
YieldReaction ConditionsOperation in experiment
92% With sodium acetate for 3h; Heating;
  • 6
  • [ 5355-17-9 ]
  • [ 999-97-3 ]
  • [ 180521-88-4 ]
YieldReaction ConditionsOperation in experiment
98% With sulfuric acid for 4h; Heating;
  • 7
  • [ 221897-54-7 ]
  • [ 5355-17-9 ]
  • [ 221897-55-8 ]
YieldReaction ConditionsOperation in experiment
72% With potassium carbonate In methanol; water at 25℃; for 2h; other substrate: (3S,4S,5S,7aR)-(-)-3,5-bis(2-methoxyphenyl)-4-<(4-acetyloxyphenyl)methyl>pyrrolizidinium chloride;
  • 8
  • [ 67-56-1 ]
  • [ 106-44-5 ]
  • [ 23438-17-7 ]
  • [ 5355-17-9 ]
YieldReaction ConditionsOperation in experiment
1: 66% 2: 10% With [bis(acetoxy)iodo]benzene at 20℃; for 4h;
  • 9
  • [ 5355-17-9 ]
  • [ 136590-83-5 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Stage #1: 4-hydroxybenzyl methyl ether With potassium <i>tert</i>-butylate In tetrahydrofuran at 25℃; for 1h; Stage #2: 3,5-dichloropyridine-4-carboxaldehyde In tetrahydrofuran at 70℃; for 2h; Further stages.;
  • 10
  • [ 67-56-1 ]
  • [ 106-44-5 ]
  • [ 5355-17-9 ]
  • [ 123-08-0 ]
  • [ 99-76-3 ]
  • [ 99-96-7 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; oxygen at 74.84℃; for 3h;
  • 11
  • [ 5355-17-9 ]
  • [ 3188-13-4 ]
  • [ 675855-49-9 ]
YieldReaction ConditionsOperation in experiment
85% Stage #1: 4-hydroxybenzyl methyl ether With sodium hydride In tetrahydrofuran at 20℃; for 4h; Stage #2: ethyl chloromethyl ether In tetrahydrofuran at 20℃; Further stages.;
  • 12
  • [ 67-56-1 ]
  • [ 623-05-2 ]
  • [ 5355-17-9 ]
  • [ 1515-81-7 ]
YieldReaction ConditionsOperation in experiment
95% With sodium hydrogen sulfate; silica gel In dichloromethane at 20℃; for 1.5h;
  • 13
  • [ 5355-17-9 ]
  • [ 123-08-0 ]
YieldReaction ConditionsOperation in experiment
94% With hydrogen bromide; dimethyl sulfoxide at 110℃; for 5h;
86.1% 40 EXAMPLE 40 Conversion>99%. Yield: 86.1% of p-hydroxybenzaldehyde; 1.7% of p-hydroxybenzyl methyl ether.
85.3% 39 EXAMPLE 39 Conversion>99%. Yield: 85.3% of p-hydroxybenzaldehyde; 2.6% of p-hydroxybenzyl methyl ether.
70.4% 38 EXAMPLE 38 Conversion>99%. Yield: 70.4% of p-hydroxybenzaldehyde; 0.5% of p-hydroxybenzyl methyl ether.

  • 14
  • [ 5355-17-9 ]
  • [ 35117-05-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: NaH / tetrahydrofuran / 4 h / 20 °C 1.2: 85 percent / tetrahydrofuran / 20 °C 2.1: Li; naphthalene / tetrahydrofuran / 2 h / -10 °C 2.2: 95 percent Spectr. / H2O / tetrahydrofuran / 0.5 h / -10 °C
 

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