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Chemical Structure| 459-60-9 Chemical Structure| 459-60-9

Structure of 4-Fluoroanisole
CAS No.: 459-60-9

Chemical Structure| 459-60-9

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Product Details of [ 459-60-9 ]

CAS No. :459-60-9
Formula : C7H7FO
M.W : 126.13
SMILES Code : COC1=CC=C(F)C=C1
MDL No. :MFCD00000348
InChI Key :VIPWUFMFHBIKQI-UHFFFAOYSA-N
Pubchem ID :9987

Safety of [ 459-60-9 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225
Precautionary Statements:P210-P403+P235
Class:3
UN#:3271
Packing Group:

Computational Chemistry of [ 459-60-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 32.89
TPSA ?

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

9.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.02
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

2.26
Log Po/w (WLOGP)?

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

2.25
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.

2.24
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

2.26
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.21

Water Solubility

Log S (ESOL):?

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

-2.47
Solubility 0.424 mg/ml ; 0.00336 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.

-2.09
Solubility 1.02 mg/ml ; 0.00812 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

-2.76
Solubility 0.218 mg/ml ; 0.00173 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.

-5.46 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

2.0
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)

1.09

Application In Synthesis of [ 459-60-9 ]

* 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.

  • Upstream synthesis route of [ 459-60-9 ]
  • Downstream synthetic route of [ 459-60-9 ]

[ 459-60-9 ] Synthesis Path-Upstream   1~4

  • 1
  • [ 459-60-9 ]
  • [ 3522-07-4 ]
References: [1] Tetrahedron Letters, 2004, vol. 45, # 8, p. 1769 - 1771.
  • 2
  • [ 459-60-9 ]
  • [ 75-36-5 ]
  • [ 445-82-9 ]
YieldReaction ConditionsOperation in experiment
89% With aluminum (III) chloride In dichloromethane at 1 - 5℃; for 19 h; Inert atmosphere [00206] Example 3.9: Two-Step Preparation of 2-chloro-l-(5-fluoro-2- methoxyphenyl)ethanone (compound 1) [00207] Compound 1 in Scheme 4 was generally prepared in a two-step procedure according to Scheme 5 below.Scheme 5: Synthetic scheme for the preparation of Compound 1 of Scheme 4 [00208] Step 1. A 125-mL three-necked jacketed reaction flask fitted with a temperature probe and nitrogen balloon was charged with aluminum chloride (12.7 g, 95.1 mmol) and dichloromethane (50 mL). This mixture was cooled to 1-2 °C and 4-fluoroanisole (compound 9, 8.98 mL, 79.3 mmol) was added slowly over a period of 30 minutes to maintain the temperature below 5 °C. After the mixture had re-cooled to 1-2 °C, neat acetyl chloride (7.89 mL, 1 1 1 mmol) was added dropwise over a period of 30 minutes, maintaining the temperature below 5 °C. The reaction was then allowed to stir at 1-2 °C for 18 hours. [00209] A 1-L three-necked round bottom flask fitted with a temperature probe and mechanical stirrer was charged with sodium hydroxide (20.2 g, 504 mmol) and water (200 mL) followed by the slow addition of acetic acid (28.7 mL, 504 mmol) while cooling in an ice bath. The homogeneous Friedel-Crafts mixture was diluted with dichloromethane (25 mL) and slowly added dropwise via cannula to this cold (0-5 °C) solution of sodium acetate at a rate that maintained the temperature below 8 °C. Dichloromethane (100 mL) was added after the addition was complete and the mixture allowed to warm to room temperature and stirred for 60 minutes. This solution was transferred to an addition funnel, the layers were separated and the aqueous layer was extracted with dichloromethane (2 x 100 mL). The organics were combined, washed with IN NaOH (3 x 75 mL), dried with anhydrous sodium sulfate and concentrated. This provided 11.9g (89percent yield, 96 areapercent) of compound 10 as an oil. NMR (400 MHz, CDCh) δ ppm 2.64 (s, 3 H) 3.92 (s, 3 H) 6.94 (dd, J=9.09, 4.04 Hz, 1H) 7.18 (ddd, J=9.09, 7.33, 3.28 Hz, 1H) 7.48 (dd, J=8.97, 3.16 Hz, 1H); HPLC Retention Time: 3.39 min; MS (ESI+) for C9H9FO2 m/z 169.1 (M+H)+.
References: [1] Patent: WO2018/161008, 2018, A1, . Location in patent: Paragraph 00206-00209.
  • 3
  • [ 459-60-9 ]
  • [ 75-36-5 ]
  • [ 445-82-9 ]
  • [ 394-32-1 ]
References: [1] Journal of Organic Chemistry, 1954, vol. 19, p. 1617,1621[2] Bulletin de la Societe Chimique de France, 1956, p. 629,632.
[3] Patent: WO2018/161008, 2018, A1, . Location in patent: Paragraph 00211-00216.
  • 4
  • [ 459-60-9 ]
  • [ 445-82-9 ]
References: [1] Patent: WO2018/161008, 2018, A1, .
 

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