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Chemical Structure| 19500-02-8

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Product Details of [ 19500-02-8 ]

CAS No. :19500-02-8
Formula : C8H11NO
M.W : 137.18
SMILES Code : COC1=CC=CC(=C1C)N
MDL No. :MFCD06412568
InChI Key :OPXLVWLFDKRYRB-UHFFFAOYSA-N
Pubchem ID :11804822

Safety of [ 19500-02-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 19500-02-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
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 42.3
TPSA ?

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

35.25 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.74
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

2.22
Log Po/w (WLOGP)?

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

1.59
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.

1.48
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

1.56
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.72

Water Solubility

Log S (ESOL):?

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

-2.47
Solubility 0.468 mg/ml ; 0.00341 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.

-2.6
Solubility 0.348 mg/ml ; 0.00254 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

-2.52
Solubility 0.411 mg/ml ; 0.003 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.

-5.56 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

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<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 [ 19500-02-8 ]

* 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 [ 19500-02-8 ]

[ 19500-02-8 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 4837-88-1 ]
  • [ 19500-02-8 ]
YieldReaction ConditionsOperation in experiment
100% With hydrogen;5%-palladium/activated carbon; In ethanol; at 20℃; for 3.0h; (Referential Example 42) Synthesis of 3-amino-2-methylanisole (referential compound 42-1) A suspension of 9.98 g of 5% palladium-carbon (wet) in 100 ml of ethanol was added to a solution of 30.7 g (184 mmol) of 2-methyl-3-nitroanisole in 300 ml of ethanol and the mixture was stirred for 3 hours at room temperature in a hydrogen atmosphere. After the reaction was finished, the reaction solution was filtered through Celite and the filtrate was concentrated in vacuo to give 25.5 g of the title compound as a slightly purple oily substance (yield: quantitative). Rf value: 0.38 (n-hexane: ethyl acetate = 2:1 (v/v)) Mass spectrum (EI, m/z): 137 (M+) 1H-NMR spectrum (CDCl3, delta ppm): 2.04-2.05 (m, 3H), 3.60 (brs, 2H), 3.80 (s, 3H), 6.33-6.37 (m, 2H), 6.94-7.01 (m, 1H)
100% With hydrogen;5%-palladium/activated carbon; In ethanol; water; at 20℃; for 3.0h; A suspension of 9.98 g of 5% palladium-carbon (hydrous) in 100 ml of ethanol was added to a solution of 30.7 g (184 mmol) of 2-methyl-3-nitroanisole in 300 ml of ethanol and the mixture was stirred for 3 hours at room temperature in a hydrogen atmosphere. After the reaction was completed, the reaction solution was filtered through Celite and the filtrate was concentrated under reduced pressure, whereby 25.5 g of the title compound was obtained as a slightly purple oily substance (yield: quantitative). Rf value: 0.38 (n-hexane:ethyl acetate=2:1 (v/v)) Mass spectrum (EI, m/z): 137 (M+) 1H-NMR spectrum (CDCl3, deltappm): 2.04-2.05 (m, 3H), 3.60 (brs, 2H), 3.80 (s, 3H), 6.33-6.37 (m, 2H), 6.94-7.01 (m, 1H) (Example 1)
98% With hydrogen;palladium 10% on activated carbon; In ethanol; at 18 - 22℃; for 19.0h; To a solution of 2-methyl-3-nitro ANISOLE A1 (5. 1 g; 30. 33 mmol ; requires-30 min to dissolve) in absolute ethanol (85 mL) was added 10% Pd/C catalyst (500 mg). The solution was hydrogenated under a hydrogen filled balloon at atmospheric pressure and room temperature for 19 h. The reaction mixture was filtered through a Celite pad, rinsed and evaporated to dryness to obtain 2-methyl-3-methoxyaniline A2 as a deep mauve oil (4.1 g; 29.81 mmol ; 98 % YIELD).. MS 137 (MH) +. Reverse Phase HPLC Homogeneity 220 rim (0.06 % TFA; CH3CN : H20) : 99%.
98% With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; for 19.0h; EXAMPLE 1A- SYNTHESIS OF P2 BUILDING BLOCK 2-METHYL-3-METHOXY ANILINE (1A2); EtOHPd/C(10%)H21a1 1a2To a solution of 2-methyl-3-nitro anisole which is commercially available (1a1) (5.1 g;30.33 mmol; requires -30 min. to dissolve) in absolute ethanol (85 ml_) was added10% Pd/C catalyst (500 mg). The solution was hydrogenated under a hydrogen filledballoon at atmospheric pressure and room temperature for 19 h. The reaction mixturewas filtered through a Celite pad, rinsed and evaporated to dryness to obtain thecompound 1a2 as a deep mauve oil (4.1 g; 29.81 mmol; 98% yield). MS 137 (MH)+.Reverse Phase HPLC Homogeneity (at) 220nm (0.06 % TFA;CH3CN;H2O): 99%.
98% With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; under 760.051 Torr; for 19.0h; To a solution of 2-methyl-3-nitro anisole which is commercially available (1a1) (5.1 g; 30.33 mmol; requires ~30 min. to dissolve) in absolute ethanol (85 mL) was added 10% Pd/C catalyst (500 mg). The solution was hydrogenated under a hydrogen filled balloon at atmospheric pressure and room temperature for 19 h. The reaction mixture was filtered through a Celite pad, rinsed and evaporated to dryness to obtain the compound 1a2 as a deep mauve oil (4.1 g; 29.81 mmol; 98% yield). MS 137 (MH)+. Reverse Phase HPLC Homogeneitya220nm (0.06% TFA;CH3CN;H2O): 99%.
98% With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; for 19.0h; To a solution of 2-methyl-3-nitro anisole which is commercially available (2a1) (5.1g ;30.33mmol ; requires ~30min. to dissolve) in absolute ethanol (85mL) was added 10%Pd/C catalyst (500mg) . The solution was hydrogenated under a hydrogen filledballoon at atmospheric pressure and room temperature for 19 hrs. The reactionmixture was filtered through a Celite pad, rinsed and evaporated to dryness to obtainthe compound 2a2 as a deep mauve oil (4.1g ; 29.81mmol ; 98 % yield). MS 137(MH)+. Reverse Phase HPLC Homogeneity (at) 220nm (0.06 % TFA;CH3CN;H20):99%.
98% With hydrogen;palladium 10% on activated carbon; In ethanol; at 18 - 22℃; under 760.051 Torr; for 19.0h; EXAMPLE 2A; Synthesis of 1-methyl-2-methoxy aniline (2A2); To a solution of 2-methyl-3-nitro anisole (2A1) (5.1 g ; 30.33 mmol ; requires ~30min. to dissolve) in absolute ethanol (85 mL) was added 10% Pd/C catalyst (500 mg) . The solution was hydrogenated under a hydrogen filled balloon at atmospheric pressure and room temperature for 19 h. The reaction mixture was filtered through a Celite pad, rinsed and evaporated to dryness to obtain the compound 2A2 as a deep mauve oil (4.1 g ; 29.81 mmol ; 98% yield).MS 137 (MH)+. Reverse Phase HPLC Homogeneity (at) 220nm (0.06 % TFA ; CH3CN : H2O) : 99%.
96% With formic acid; hydrazine; zinc; In methanol; at 5 - 61℃; for 2.0h; EXAMPLE 4: SYNTHESIS OF ILY-4001 [2-(3-(2-AMINO^-OXOACETYL)-I-(BIPHENYL-2-YLMETHYL)-2-METHYL-1H-INDOL-4-YLOXY)ACETIC ACID] (ME INDOXAM). [020112-Methyl-3-methoxyaniline (2) [04-035-11]. To a stirred cooled (ca. 50C) hydrazine hydrate (159.7 g, 3.19 mol), 85% formic acid (172.8 g, 3.19 mol) was added drop wise at 10 - 2O0C. The resultant mixture was added drop wise to a stirred suspension of zinc dust (104.3 g, 1.595 mol) in a solution of 2-methyl-3-nitroanisole (1) (53.34 g, 0.319 mol) in methanol (1000 mL). An exothermic reaction occurred. After the addition was complete, the reaction mixture was stirred for additional 2 h (until temperature dropped from 61 C to RT) and the precipitate was filtered off and washed with methanol (3x150 mL). The filtrate was concentrated under reduced pressure to a volume of ca. 250 mL. The residue was treated with EtOAc (500 ml) and saturated aqueous NaHCO3 (500 mL). The aqueous phase was separated off and discarded. The organic phase was washed with water (300 mL) and extracted with 1 N HCI (800 mL). The acidic extract was washed with EtOAc (300 mL) and was basisified with K2CO3 (90 g). The free base 2 was extracted with EtOAc (3x200 mL) and the combined extracts were dried over MgSO4. After filtration and removal of the solvent from the filtrate, product 2 was obtained as a red oil, which was used in the next step without further purification. Yield: 42.0 g (96%).
96% With formic acid; hydrazine; zinc; In methanol; at 20 - 61℃; for 2.0h; 2-Methyl-3-methoxyaniline (2); [04-035-11]. To a stirred cooled (ca. 5C) hydrazine hydrate (159.7 g, 3.19 mol), 85% formic acid (172.8 g, 3.19 mol) was added drop wise at 10 - 2O0C. The resultant mixture was added drop wise to a stirred suspension of zinc dust (104.3 g, 1.595 mol) in a solution of 2-methyl-3-nitroanisole (1) (53.34 g, 0.319 mol) in methanol (1000 mL). An exothermic reaction occurred. After the addition was complete, the reaction mixture was stirred for additional 2 h (until temperature dropped from 61 C to RT) and the precipitate was filtered off and washed with methanol (3x150 mL). The filtrate was concentrated under reduced pressure to a volume of ca. 250 mL. The residue was treated with EtOAc (500 ml) and saturated aqueous NaHCO3 (500 mL). The aqueous phase was separated off and discarded. The organic phase was washed with water (300 mL) and extracted with 1 N HCI (800 mL). The acidic extract was washed with EtOAc (300 mL) and was basisified with K2CO3 (90 g). The free base 2 was extracted with EtOAc (3x200 mL) and the combined extracts were dried over MgSO4. After filtration and removal of the solvent from the filtrate, product 2 was obtained as a red oil, which was used in the next step without further purification. Yield: 42.0 g (96%).
96% [00305] 2-Methyl-3-methoxyaniline (2) [04-035-11]. To a stirred cooled (ca. 5C) hydrazine hydrate (159.7 g, 3.19 mol), 85% formic acid (172.8 g, 3.19 mol) was added drop wise at 10 - 200C. The resultant mixture was added drop wise to a stirred suspension of zinc dust (104.3 g, 1.595 mol) in a solution of 2-methyl-3-nitroanisole (1) (53.34 g, 0.319 mol) in methanol (1000 mL). An exothermic reaction occurred. After the addition was complete, the reaction mixture was stirred for additional 2 h (until temperature dropped from 61 C to RT) and the precipitate was filtered off and washed with methanol (3x150 mL). The filtrate was concentrated under reduced pressure to a volume of ca. 250 mL. The residue was treated with EtOAc (500 ml) and saturated aqueous NaHCO3 (500 mL). The aqueous phase was separated off and discarded. The organic phase was washed with water (300 mL) and extracted with 1 N HCI (800 mL). The acidic extract was washed with EtOAc (300 mL) and was basisified with K2CO3 (90 g). The free base 2 was extracted with EtOAc (3x200 mL) and the combined extracts were dried over IVIgSO4. After filtration and removal of the solvent from the filtrate, product 2 was obtained as a red oil, which was used in the next step without further purification. Yield: 42.0 g (96%).
96% With formic acid; hydrazine; zinc; In methanol; at 61℃; for 2.0h; 2-Methyl-3-methoxyaniline (2) [04-035-11]. ; To a stirred cooled (ca. 5C) hydrazine hydrate (159.7 g, 3.19 mol), 85% formic acid (172.8 g, 3.19 mol) was added drop wise at 10 - 20C. The resultant mixture was added drop wise to a stirred suspension of zinc dust (104.3 g, 1.595 mol) in a solution of 2-methyl-3-nitroanisole (1) (53.34 g, 0.319 mol) in methanol (1000 mL). An exothermic reaction occurred. After the addition was complete, the reaction mixture was stirred for additional 2 h (until temperature dropped from 61 C to RT) and the precipitate was filtered off and washed with methanol (3x150 mL). The filtrate was concentrated under reduced pressure to a volume of ca. 250 mL. The residue was treated with EtOAc (500 ml) and saturated aqueous NaHCO3 (500 mL). The aqueous phase was separated off and discarded. The organic phase was washed with water (300 mL) and extracted with 1N HCI (800 mL). The acidic extract was washed with EtOAc (300 mL) and was basisified with K2CO3 (90 g). The free base 2 was extracted with EtOAc (3x200 mL) and the combined extracts were dried over MgSO^ After filtration and removal of the solvent from the filtrate, product 2 was obtained as a red oil, which was used in the next step without further purification. Yield: 42.0 g (96%).
96% To a stirred cooled (ca. 5 C.) hydrazine hydrate (159.7 g, 3.19 mol), 85% formic acid (172.8 g, 3.19 mol) was added drop wise at 10-20 C. The resultant mixture was added drop wise to a stirred suspension of zinc dust (104.3 g, 1.595 mol) in a solution of 2-methyl-3-nitroanisole (1) (53.34 g, 0.319 mol) in methanol (1000 mL). An exothermic reaction occurred. After the addition was complete, the reaction mixture was stirred for additional 2 h (until temperature dropped from 61 C. to RT) and the precipitate was filtered off and washed with methanol (3×150 mL). The filtrate was concentrated under reduced pressure to a volume of ca. 250 mL. The residue was treated with EtOAc (500 ml) and saturated aqueous NaHCO3 (500 mL). The aqueous phase was separated off and discarded. The organic phase was washed with water (300 mL) and extracted with 1N HCl (800 mL). The acidic extract was washed with EtOAc (300 mL) and was basisified with K2CO3 (90 g). The free base 2 was extracted with EtOAc (3×200 mL) and the combined extracts were dried over MgSO4. After filtration and removal of the solvent from the filtrate, product 2 was obtained as a red oil, which was used in the next step without further purification. Yield: 42.0 g (96%).
In aluminum nickel; ethanol; 3-Methoxy-2-methyl-aniline 200 gm (1.19 mols) of 2-methoxy-6-nitro-toluene were hydrogenated in 2.5 liters of ethanol in the presence of 25 gm of Raney nickel at 100 bar until the absorption of the calculated amount of hydrogen. The reaction mixture was filtered and evaporated in vacuo. After distillation 158.3 gm (97% of theory) of 3-methoxy-2-methylaniline were obtained. B.p.: 126 C. at 16.25 mbar.
With hydrogen;5%-palladium/activated carbon; In methanol; at 20℃; 2-Methoxy-6-aminotoluene; 2-methyl-3-nitroanisole (20 g, 0.12 mol) was suspended in methanol (200 ml) at RT under nitrogen. Pd/C (5%, 2 g) was added and the system was shaken under an atmosphere of hydrogen overnight, until TLC indicated one product. The reaction mixture was filtered through celite, and the celite washed with methanol (3 x 100 ml) and the filtrate concentrated in vacuo. This afforded 18 g of a red oil that was used without further purification. No.H (CDCl3; 250MHz) 7.01 (1 H, t, J 8, aromatics), 6.38 (2H, d, J 8, aromatics), 3.83 (3H, s, OCH3), 2.08 (3H, s, CH3).
With hydrogen;palladium 10% on activated carbon; In ethanol; for 6.0h; A mixture of 2-methyl-3-nitroanisole (16.7 g), 10 % Pd-C (1.6 g) and ethanol (330 ml) was stirred in hydrogen atmosphere for 6 hours. The insoluble residue was filtrated and the filtrate was concentrated under reduced pressure to give a title compound (12.5 g). NMR (CDCl3): delta 2.04(3H,s), 3.71(3H,s), 6.33-6.36(2H,m), 6.94-7.00(1H,m).
With hydrogen;5% palladium over charcoal; In ethanol; at 20℃; for 3.0h; (Reference Example 27) Synthesis of 3-amino-2-methylanisole (Reference compound 27) A suspension of 9.98 g of 5% palladium-carbon (hydrous) in 100 ml of ethanol was added to a solution of 30.7 g (184 mmol) of 2-methyl-3-nitroanisole in 300 ml of ethanol and the mixture was stirred for 3 hours at room temperature in a hydrogen atmosphere. After the reaction was completed, the reaction solution was filtered through Celite and the filtrate was concentrated under reduced pressure, whereby 25.5 g of the title compound was obtained as a slightly purple oily substance (yield: quantitative). Rf value: 0.38 (n-hexane: ethyl acetate = 2: 1 (v/v)) Mass spectrum (EI, m/z): 137 (M+) 1H-NMR spectrum (CDCl3, deltappm): 2.04-2.05 (m, 3H), 3.60 (brs, 2H), 3.80 (s, 3H), 6.33-6.37 (m, 2H), 6.94-7.01 (m, 1H)
With hydrogen;palladium 10% on activated carbon; for 1.0h; Intermediate 58methyloxy)anilineTo a solution of 2-methyl-1 -(methyloxy)-3-nitrobenzene (Intermediate 57, 1.67 g) in methanol (50 mL) was added Pd/C (10%, 50 mg) and the reaction mixture was stirred under H2 atmosphere for 1 hour. The mixture was filtered through a pad of celite. Evaporation afforded the title compound as a solid (1.31 g).
8.59 g With palladium 10% on activated carbon; hydrogen; In ethyl acetate; at 20℃; for 6.0h; Methyl iodide (8.13 mL, 130.6 mmol) was added dropwise to a solution of 8 (10 g, 65.29 mmol) ,and potassium carbonate (18.05 g, 130.6 mmol) in anhydrous DMF (130 mL). The reaction mixture was stirred at rt for 14 h and quenched by the addition of H2O (250 mL). The aqueous phase was extracted with EtOAc (3 × 200 mL), the combined organic layers washed with water (100 mL), saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated to give corresponding methyl ether as a colorless solid. Palladium on carbon (10%, 200 mg) was added to a solution of above product in EtOAc (130 mL). The suspension was stirred at rt for 6 h under a hydrogen atmosphere before it was filtered through a plug of celite and eluted with EtOAc (150 mL). The eluent was concentrated to afford 12 (8.59 g, 96% over two steps) as a colorless amorphous solid: 1H NMR (500 MHz, CDCl3) delta 6.97 - 6.83 (m, 1H), 6.37 - 6.20 (m, 2H), 3.72 (s, 3H), 3.54 (br s, 2H), 1.97 (s, 3H); 13C NMR (125 MHz, CDCl3) delta 158.2, 145.6, 126.5, 110.4, 108.4, 101.2, 55.6, 8.9.

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Chemical Structure| 41280-55-1

A126476 [41280-55-1]

4-(2,6-Dimethylphenoxy)aniline

Similarity: 0.89

Chemical Structure| 91251-42-2

A242752 [91251-42-2]

3-Isopropyl-4-methoxyaniline

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Chemical Structure| 1154942-83-2

A998031 [1154942-83-2]

3-(2-Methoxyethoxy)-4-methylaniline

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Ethers

Chemical Structure| 136-90-3

A131237 [136-90-3]

4-Methoxy-3-methylphenylamine

Similarity: 0.98

Chemical Structure| 50868-72-9

A162290 [50868-72-9]

5-Methoxy-2-methylaniline

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Chemical Structure| 41280-55-1

A126476 [41280-55-1]

4-(2,6-Dimethylphenoxy)aniline

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Chemical Structure| 91251-42-2

A242752 [91251-42-2]

3-Isopropyl-4-methoxyaniline

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Chemical Structure| 1154942-83-2

A998031 [1154942-83-2]

3-(2-Methoxyethoxy)-4-methylaniline

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Amines

Chemical Structure| 136-90-3

A131237 [136-90-3]

4-Methoxy-3-methylphenylamine

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Chemical Structure| 50868-72-9

A162290 [50868-72-9]

5-Methoxy-2-methylaniline

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Chemical Structure| 41280-55-1

A126476 [41280-55-1]

4-(2,6-Dimethylphenoxy)aniline

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A242752 [91251-42-2]

3-Isopropyl-4-methoxyaniline

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Chemical Structure| 1154942-83-2

A998031 [1154942-83-2]

3-(2-Methoxyethoxy)-4-methylaniline

Similarity: 0.89