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Structure of 504414-32-8

Chemical Structure| 504414-32-8

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Product Details of [ 504414-32-8 ]

CAS No. :504414-32-8
Formula : C14H11FO2
M.W : 230.23
SMILES Code : FC1=C(C=O)C=CC(OCC2=CC=CC=C2)=C1
MDL No. :MFCD12025062
InChI Key :KRCUZBWXZUPORH-UHFFFAOYSA-N
Pubchem ID :12136989

Safety of [ 504414-32-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 504414-32-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 12
Fraction Csp3 0.07
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 62.77
TPSA ?

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

26.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.48
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

2.95
Log Po/w (WLOGP)?

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

3.49
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.

3.0
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

3.98
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.18

Water Solubility

Log S (ESOL):?

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

-3.38
Solubility 0.095 mg/ml ; 0.000413 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.

-3.16
Solubility 0.158 mg/ml ; 0.000684 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

-5.29
Solubility 0.00117 mg/ml ; 0.00000507 mol/l
Class?

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

Moderately 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

Yes
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

Yes
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.

-5.61 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

0.0
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)

1.84

Application In Synthesis of [ 504414-32-8 ]

* 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 [ 504414-32-8 ]

[ 504414-32-8 ] Synthesis Path-Downstream   1~26

  • 2
  • diisobutylaluminum hydride [ No CAS ]
  • [ 185836-35-5 ]
  • [ 504414-32-8 ]
YieldReaction ConditionsOperation in experiment
88% With hydrogenchloride; In dichloromethane; 4-Benzyloxy-2-fluoro-benzaldehyde (Compound 8) A stirred, cooled (-78 C.) solution of 4-benzyloxy-2-fluoro-benzonitrile (Compound 7, 18 g, 79 mmol) in dichloromethane (50 mL) was treated with a 1M solution of di-isobutyl aluminum hydride in hexanes (100 mL, 100 mmol). The reaction mixture was allowed to warm to ambient temperature over 1 h. It was then quenched with aqueous dilute hydrochloric acid and extracted with diethyl ether (*2). The combined organic phase was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to afford the title product as a white solid (16 g, 88%). 1H-NMR (300 MHz, CDCl3): delta5.11 (s, 2H), 6.70 (dd, J=12.3, 2.3 Hz, 1H), 6.82-6.86 (m, 1H), 7.24-7.42 (m, 5H), 7.81 (t, J=8.9 Hz, 1H), 10.19 (s, 1H).
88% With hydrogenchloride; In dichloromethane; 4-Benzyloxy-2-fluoro-benzaldehyde (Compound 8) A stirred, cooled (-78 C.) solution of 4-benzyloxy-2-fluoro-benzonitrile (Compound 7, 18 g, 79 mmol) in dichloromethane (50 mL) was treated with a 1M solution of di-isobutyl aluminum hydride in hexanes (100 mL, 100 mmol). The reaction mixture was allowed to warm to ambient temperature over 1 h. It was then quenched with aqueous dilute hydrochloric acid and extracted with diethyl ether (*2). The combined organic phase was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to afford the title product as a white solid (16 g, 88%). 1H-NMR (300 MHz, CDCl3): delta 5.11(s, 2H), 6.70(dd, J=12.3, 2.3 Hz, 1H), 6.82-6.86(m, 1H), 7.24-7.42(m, 5H), 7.81(t, J=8.9 Hz, 1H), 10.19(s, 1H).
  • 3
  • [ 504414-32-8 ]
  • [ 504414-33-9 ]
YieldReaction ConditionsOperation in experiment
95% With sodium borohydrid; In methanol; dichloromethane; 4-Benzyloxy-2-fluoro-benzyl alcohol (Compound 9) A solution of 4-benzyloxy-2-fluoro benzaldehyde (Compound 8, 16 g, 69.6 mmol) in methanol (100 mL) and dichloromethane (100 mL) was treated with sodium borohydride (5.26 g, 139 mmol). After 2 h at ambient temperature, the volatiles were evaporated in vacuo, the residue was diluted with water and dilute aqueous hydrochloric acid and extracted with diethyl ether (*2). The combined organic phase was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to afford the title product as a white solid (15 g, 95%). 1H-NMR (300 MHz, CDCl3): delta2.13 (s, 1H), 4.61 (s, 2H), 5.01 (s, 2H), 6.64-6.74 (m, 2H), 7.25 (t, J=8.2 Hz, 1H), 7.29-7.42 (m, 5H).
95% With sodium tetrahydroborate; In methanol; dichloromethane; at 20℃; for 2h; A solution of 4-benzyloxy-2-fluoro benzaldehyde (Compound 8, 16 g, 69.6 mmol) in methanol (100 mL) and dichloromethane (100 mL) was treated with sodium borohydride (5.26 g, 139 mmol). After 2 h at ambient temperature, the volatiles were evaporated in vacuo, the residue was diluted with water and dilute aqueous hydrochloric acid and extracted with diethyl ether (*2). The combined organic phase was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to afford the title product as a white solid (15 g, 95%). [0121] <1>H-NMR (300 MHz, CDCl3): [delta]2.13(s, 1H), 4.61(s, 2H), 5.01(s, 2H), 6.64-6.74(m, 2H), 7.25(t, J=8.2 Hz, 1H), 7.29-7.42(m, 5H).
With sodium borohydrid; In methanol; dichloromethane; 4-Benzyloxy-2-fluoro-benzyl alcohol (Compound 9) A solution of 4-benzyloxy-2-fluoro benzaldehyde (Compound 8, 16 g, 69.6 mmol) in methanol (100 mL) and dichloromethane (100 mL) was treated with sodium borohydride (5.26 g, 139 mmol). After 2 h at ambient temperature, the volatiles were evaporated in vacuo, the residue was diluted with water and dilute aqueous hydrochloric acid and extracted with diethyl ether (*2). The combined organic phase was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to afford the title product as a white solid (l5 g, 95%). 1H-NMR (300 MHz, CDCl3): delta 2.13(s, 1H), 4.61(s, 2H), 5.01(s, 2H), 6.64-6.74(m, 2H), 7.25(t, J=8.2 Hz, 1H), 7.29-7.42(m, 5H).
  • 4
  • [ 185836-35-5 ]
  • [ 504414-32-8 ]
YieldReaction ConditionsOperation in experiment
88% With diisobutylaluminium hydride; In hexanes; dichloromethane; at -78 - 20℃; for 1h; A stirred, cooled (-78[deg.] C.) solution of 4-benzyloxy-2-fluoro-benzonitrile (Compound 7, 18 g, 79 mmol) in dichloromethane (50 mL) was treated with a 1M solution of di-isobutyl aluminum hydride in hexanes (100 mL, 100 mmol). The reaction mixture was allowed to warm to ambient temperature over 1 h. It was then quenched with aqueous dilute hydrochloric acid and extracted with diethyl ether (*2). The combined organic phase was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to afford the title product as a white solid (16 g, 88%). [0118] <1>H-NMR (300 MHz, CDCl3): [delta]5.11 (s, 2H), 6.70(dd, J=12.3, 2.3 Hz, 1H), 6.82-6.86(m, 1H), 7.24-7.42(m, 5H), 7.81(t,J=8.9 Hz, 1H), 10.19(s, 1H).
  • 5
  • [ 348-27-6 ]
  • [ 100-39-0 ]
  • [ 504414-32-8 ]
YieldReaction ConditionsOperation in experiment
94.4% With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 72h; Example 2: 10-acetyl-l l-(4-benzyloxy-2-fluorophenyl)-3,3-dimethyl-l,l-dioxo- 1,2,3,4,5,1 l-hexahvdro-llambda6-thia-5J0-diazadibenzoralpha,?cvcloheptene (13); Step 1; A mixture of 2-fluoro-4-hydroxybenzaldehyde (2.92 mmol), benzylbromide (534 muL, 4.38 mmol) and Cs2CO3 (1.14 g, 3.50 mmol) in dry DMF (N,N-dimethylformamide; <n="51"/>10 niL) was stirred at room temperature for 3 days. Then, the reaction mixture was diluted with water (200 mL). The resulting precipitate was filtered off, then dried under vacuum to give the desired product 4-benzyloxy-2-fluorobenzaldehyde (11) (94.4 %) as a white solid: m/z = 231 (M+H)+.
  • 6
  • [ 504414-32-8 ]
  • [ 1049093-57-3 ]
  • [ 28920-43-6 ]
  • [ 1049093-59-5 ]
YieldReaction ConditionsOperation in experiment
21% To a mixture of regioisomers (350) and (351) (3200 mg, 5.67 mmol) in DMF (200 mL) was added Fmoc-CI (9-fluorenylmethyl carbamate chloride; 1468 mg, 1 eq). The reaction mixture was then heated at 500C for Ih. Aldehyde (11) (1306 mg, 1 eq) and NaHCtheta3 (477 mg, 1 eq) were then added and the reaction mixture was further heated for 16h, then was then filtered on decalite, diluted with a saturated aqueous solution of NaHCtheta3 and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated. Purification of the crude by flash chromatography on silical gel (eluent: CF^C^/ethyl acetate) afforded 1200 mg (21% overall yield) of the target product [1 l-(4-Benzyloxy-2-fluoro-phenyl)-3,3-dimethyl- l,l-dioxo-2, 3,4, 5, 10,11 -hexahydro- IH-I lambda6-thia-5,l 0-diaza-dibenzo[a,d]cyclohepten- 6-yl]-carbamic acid 9H-fluoren-9-ylmethyl ester (352); m/z = 716 (M+eta)+.
  • 7
  • [ 504414-32-8 ]
  • [ 1049093-45-9 ]
  • C27H27ClN2O3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With toluene-4-sulfonic acid; In dimethyl sulfoxide; at 75℃; for 4h; Step 2; A solution of the enamine (7) (159 mg, 0.597 mmol),/?-TSA (5 mg, 0.030 mmol) and the aldehyde (11) (137 mg, 0.597 mmol) in DMSO (5 mL) was heated at 75C under nitrogen. After 4h, the reaction mixture was allowed to cool down to room temperature, then diluted with water. The resulting mixture was successively extracted with CH2Cl2 and AcOEt. The resulting organic layer was successively washed with brine, dried (Na2SO4) and evaporated. The residue was triturated in water. The precipitate was collected by filtration, washed with water and dried under vacuum to give 243 mg of the target product (12): Rt = 2.48 min, m/z = 479 (M+H)+.
  • 8
  • [ 504414-32-8 ]
  • [ 1049093-50-6 ]
  • [ 1049093-49-3 ]
  • [ 1049090-47-2 ]
  • [ 1049093-95-9 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; at 50℃; for 16h; To the above reaction mixture containing (195) and (196) were added 4-benzyloxy- 2-fluorobenzaldehyde (11) (251 mg, 1 eq) and NaHCO3 (81 mg, 0.9 eq). The reaction mixture was heated at 500C for 16h. After cooling to room temperature, the reaction mixture was diluted with saturated NaHCO3 solution, extracted with CH2Cl2 several times and the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (eluent: ethyl acetate/CH2Cl2 30:70) afforded the mixture of the 2 regioisomers (197) and (198); m/z = 509 (M+H)+.
  • 9
  • [ 504414-32-8 ]
  • [ 1049093-48-2 ]
  • [ 1049093-94-8 ]
  • [ 1049088-69-8 ]
  • [ 1049088-70-1 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; at 50℃; for 12h; NaHCtheta3 (232 mg, 2.76 mmol) was added to the above reaction mixture of (16) and (17) obtained via step 1. Then, the aldehyde (11) (707 mg, 3.07 mmol) was added and <n="54"/>the resulting mixture was stirred at 500C. After 12h, the reaction mixture was successively cooled down to room temperature, filtered and washed with CH2Cl2 and saturated NaHCO3. The water layer was extracted with CH2Cl2. Combined organic layers were dried over MgSO4, filtered, and evaporated. The residue was purified by column chromatography (gradient: ethyl acetate/CH2Cl2, 20:80 to 30:70) to give 292 mg of the target product 1 l-(4-benzyloxy-2-fluorophenyl)-6-hydroxy-3,3-dimethyl- 1 , 1 -dioxo- 1,2,3,4,5,11 -hexahydro- 1 lambda6-thia-5 , 10-diazadibenzo[alpha, J]cycloheptene (18) : Rt = 2.26 min, m/z = 495 (M+H)+. 1H NMR (400 MHz, DMSO-J6) delta ppm 1.18 (s, 3H), 1.19 (s, 3 H), 2.64 (d, J= 16.2 Hz, 1 H), 2.70 (d, J= 16.2 Hz, 1 H), 3.09 (d, J= 13.4 Hz, 1 H), 3.15 (d, J= 13.4 Hz, 1 H), 4.98 (s, 2 H), 5.58 (d, J= 6.0 Hz, 1 H), 5.86 (d, J = 6.0 Hz, 1 H), 6.02 (dd, J= 7.8; 1.1 Hz, 1 H), 6.26 (dd, J= 7.8, 1.1 Hz, 1 H), 6.40 (t, J = 7.8 Hz, 1 H), 6.55 (dd, J= 8.6, 2.5 Hz, 1 H), 6.74-6.83 (2 H), 7.00 (s, 1 H), 7.27-7.44 (m, 5 H), 9.22 (s, 1 H); 13C NMR (101 MHz, DMSO-J6) ppm 27.6 (CH3), 28.3 (CH3), 31.5 (C), 43.1 (CH2), 49.3 (CH), 60.5 (CH2), 69.5 (CH2), 101.8 (CH, d, J= 25.6 Hz), 106.2 (C), 106.8 (CH), 109.6 (CH, d, J= 1.5 Hz), 111.9 (CH), 119.7 (C), 121.8 (CH), 122.7 (C, d, J= 14.6 Hz), 127.9 (CH), 128.0 (CH), 128.4 (CH), 128.8 (CH, d, J= 5.9 Hz), 136.6 (C), 137.8 (C), 143.9 (C), 146.1 (C), 158.3 (C, d, J= 11.0 Hz), 160.3 (C, d, J= 245.2 Hz); and 210 mg of 1 l-(4-benzyloxy-2-fluorophenyl)-9-hydroxy-3,3- dimethyl- 1 , 1 -dioxo- 1 ,2,3 ,4,5 , 11 -hexahydro- 1 lambda6-thia-5 , 10- diazadibenzo[alpha,
  • 10
  • [ 504414-32-8 ]
  • [ 1047619-54-4 ]
  • [ 1047618-79-0 ]
  • [ 1047618-78-9 ]
YieldReaction ConditionsOperation in experiment
With acetic acid; In ethanol;Heating / reflux; A solution of compound 71 (240 mg, 0.98 mmol) and 4-benzyloxy-2-fluoro- benzaldehyde (72) (227 mg, 1 eq) in 4 mL ethanol and 1 mL acetic acid was refluxed overnight. The reaction mixture was then concentrated and purified by preparative HPLC, yielding a mixture of the two pure title isomers 73 and 74, m/z = 459 (M+H)+.
  • 11
  • [ 504414-32-8 ]
  • [ 21204-67-1 ]
  • [ 1131871-60-7 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; for 16h;Heating / reflux; Preparation 74: (_E)-3-(4-Benzyloxy-2-fTuorophenyl)acrylic acid methyl ester; <n="47"/>(Triphenyl-lambda*5*-phosphanylidene)acetic acid methyl ester (25.0 g, 74.8 mmol) was added to a solution of <strong>[504414-32-8]4-benzyloxy-2-fluorobenzaldehyde</strong> (9.10 g, 39.5 mmol) in THF (400 inL) and the resulting solution was stirred under reflux conditions for 16 h, before being absorbed onto silica and purified by column chromotogarphy (EtOAc-IH, 1:3) to afford the title compound: RT = 4.15 min; mlz (ES+) = 287.17 [M + H]+.
In tetrahydrofuran; for 16h;Reflux; Methyl (triphenylphosphoranylidene)acetate (25.Og, 74.8mmol) was added to a solution of <strong>[504414-32-8]4-benzyloxy-2-fluorobenzaldehyde</strong> (9.1Og, 39.5mmol) in THF (40OmL) and the resulting solution was stirred under reflux conditions for 16h, before being absorbed onto silica and purified by column chromotogarphy (IH: EtOAc, 3:1) to afford the title compound: RT = 4.15 min; m/z (ES+) = 287.2 [M + H]+.
  • 12
  • [ 504414-32-8 ]
  • [ 143-33-9 ]
  • [ 1131872-14-4 ]
YieldReaction ConditionsOperation in experiment
With ammonia; ammonium chloride; In methanol; water; at 0 - 20℃; for 16.3333h; Preparation 100: Amino-(4-benzyloxy-2-fluorophenyl)acetonitrile; Ammonium chloride (948 mg, 17.72 mmol) was added to a solution of sodium cyanide (579 mg, 11.8 mmol) in ammonia (19 mL) and the resulting reaction mixture was cooled to O0C. A solution of <strong>[504414-32-8]4-benzyloxy-2-fluorobenzaldehyde</strong> (1.70 g, 7.38 mmol) in MeOH (70 mL) was added dropwise over 20 min and the reaction mixture was stirred at ambient temperature for 16 h. The solvent was removed in vacuo and the remainder was partitioned between EtOAc (100 mL) and H2O (80 mL). The aqueous phase was extracted with EtOAc (30 mL) and the combined organics were washed with H2O (50 mL), saturated aqueous NaHCO3 solution (2 X 60 mL) and brine (60 mL), dried (MgSO4), filtered and concentrated in vacuo to afford the title compound: deltaH (CDCl3) 5.01-5.07 (m, IH), 5.08 (s, 2H), 6.73-6.79 (m, IH), 6.80-6.85 (m, IH), 7.33-7.45 (m, 6H).
  • 13
  • [ 504414-32-8 ]
  • [ 371-40-4 ]
  • [ 1023328-38-2 ]
YieldReaction ConditionsOperation in experiment
98% In toluene; for 2h;Reflux; (4-Benzyloxy-2-fluorobenzylidene)(4-fluorophenyl)amine 6 6.0 g (26.1 mmol) of aldehyde 4 and 5 ml (57 mmol) of p-fluoroaniline 5 (Fluka) are boiled with 250 ml of toluene with a water trap for 2 hours, and about 150 ml of toluene are distilled out during this. The remaining toluene is concentrated in a rotary evaporator, and the residue is purified by flash chromatography (n-heptane/ethyl acetate 2:1+1% triethylamine), and 8.34 g (98% yield) of imine 6 are obtained as a crystalline solid (from n-heptane/ethyl acetate).
  • 14
  • [ 504414-33-9 ]
  • [ 504414-32-8 ]
YieldReaction ConditionsOperation in experiment
With acetic anhydride; dimethyl sulfoxide; at 20℃; for 18h; 4-Benzyloxy-2-fluorobenzaldehyde 4; 19.8 g of crude product 3 are dissolved in 200 ml of DMSO and 100 ml of acetic anhydride and left to stand at room temperature for 18 hours. This reaction solution is then diluted with 500 ml of n-heptane/ethyl acetate (2:1) and washed 3 times with saturated NaCl solution, filtered through silica gel and concentrated. Remaining acetic anhydride is evaporated off with toluene, and the residue is dissolved in a little n-heptane/ethyl acetate (2:1). 4.4 g of aldehyde 4 crystals are filtered off with suction. A further 1.6 g of crystals are obtained from the mother liquor after flash chromatography. Total yield 6 g (41% yield over 3 stages). Aldehyde 4 with molecular weight 230.24 (C14H11FO2); MS (ESI+): 231.1 (M+H+).
  • 15
  • [ 504414-32-8 ]
  • [ 1048041-42-4 ]
  • [ 1048334-68-4 ]
  • 16
  • [ 59649-56-8 ]
  • [ 504414-32-8 ]
  • [ 1049093-43-7 ]
  • [ 1049088-69-8 ]
  • [ 1049088-70-1 ]
  • 17
  • [ 504414-32-8 ]
  • [ 121056-95-9 ]
  • C22H24FNO5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% Step 1: Synthesis of Intermediate 1-24.1 R22 (22.58 g, 75.97 mmol) in Me-THF (50 mL) is cooled down to - 10C, 1,1,3,3- tetramethylguanidine (9.55 mL, 75.97 mmol) is added and stirred for 30 min. 4-benzyloxy-2- fluoro-benzaldehyde (15.9g, 69.06 mmol) dissolved in 100 mL Me-THF is added dropwise and stirred for 3h at -10C to 0C. The cooling is removed and the mixture warms up to room temperature. The reaction mixture is diluted with 300 mL Me-THF and extracted with water. The organic layer is treated with activated carbon, dried over MgS04 and concentrated. The crude product is recristallized with cyclohexane and filtered off. Yield 97%, m/z 402 [M+H]+, rt 0.80 min, LC-MS Method X018_S01.
  • 18
  • [ 504414-32-8 ]
  • C28H34FN3O5 [ No CAS ]
  • 19
  • [ 504414-32-8 ]
  • (2S)-2-amino-3-(4-benzyloxy-2-fluorophenyl)propanamide hydrochloride [ No CAS ]
  • 20
  • [ 504414-32-8 ]
  • C22H26FNO5 [ No CAS ]
  • 21
  • [ 504414-32-8 ]
  • C21H25FN2O4 [ No CAS ]
  • 22
  • [ 504414-32-8 ]
  • [ 121056-95-9 ]
  • C22H24FNO5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% R22 (22.58 g, 75.97 mmol) in Me-THF (50 mL) is cooled down to -10 C., 1,1,3,3-tetramethylguanidine (9.55 mL, 75.97 mmol) is added and stirred for 30 min. <strong>[504414-32-8]4-benzyloxy-2-fluoro-benzaldehyde</strong> (15.9 g, 69.06 mmol) dissolved in 100 mL Me-THF is added dropwise and stirred for 3 h at -10 C. to 0 C. The cooling is removed and the mixture warms up to room temperature. The reaction mixture is diluted with 300 mL Me-THF and extracted with water. The organic layer is treated with activated carbon, dried over MgSO4 and concentrated. The crude product is recrystallized with cyclohexane and filtered off. Yield 97%, m/z 402 [M+H]+, rt 0.80 min, LC-MS Method X018_S01.
  • 23
  • [ 504414-32-8 ]
  • [ 1049088-66-5 ]
  • 24
  • [ 504414-32-8 ]
  • [ 1049088-67-6 ]
  • 25
  • [ 504414-32-8 ]
  • [ 1049091-95-3 ]
  • 26
  • [ 504414-32-8 ]
  • [ 1049093-49-3 ]
  • [ 1049090-48-3 ]
 

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Technical Information

Categories

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