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Chemical Structure| 90924-12-2 Chemical Structure| 90924-12-2

Structure of 90924-12-2

Chemical Structure| 90924-12-2

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Product Details of [ 90924-12-2 ]

CAS No. :90924-12-2
Formula : C10H9NO2
M.W : 175.18
SMILES Code : OCC1=CC(=NO1)C1=CC=CC=C1
MDL No. :MFCD01928812
InChI Key :CITYOBPAADIHAD-UHFFFAOYSA-N
Pubchem ID :2763417

Safety of [ 90924-12-2 ]

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

Computational Chemistry of [ 90924-12-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 11
Fraction Csp3 0.1
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 48.07
TPSA ?

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

46.26 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.0
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

1.18
Log Po/w (WLOGP)?

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

1.68
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.

0.89
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

2.27
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.6

Water Solubility

Log S (ESOL):?

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

-2.16
Solubility 1.2 mg/ml ; 0.00686 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.

-1.75
Solubility 3.14 mg/ml ; 0.0179 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

-3.58
Solubility 0.0459 mg/ml ; 0.000262 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.

-6.53 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)

2.6

Application In Synthesis of [ 90924-12-2 ]

* 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 [ 90924-12-2 ]

[ 90924-12-2 ] Synthesis Path-Downstream   1~35

  • 3
  • [ 72418-40-7 ]
  • [ 90924-12-2 ]
  • [ 14442-12-7 ]
  • 4
  • [ 90924-12-2 ]
  • [ 39614-82-9 ]
  • [ 101576-95-8 ]
  • 5
  • [ 90924-12-2 ]
  • [ 14442-12-7 ]
YieldReaction ConditionsOperation in experiment
93% With Jones reagent; In acetone; at 20℃; for 3h; To a stirred solution of 8 (12 mg, 0.07 mmol) in acetone (0.4 ml) was added Jones? reagent (50 mul)at room temperature. Then, the mixture was stirred for 3 h. Then water (2 ml) was added, and theaqueous layer was extracted by diethyl ether (5 ml × 3). The organic layer was collected, washedwith water (5 ml × 3), dried over Na2SO4 and concentrated. The residue was recrystallized in CHCl3to afford the product (2a) as white solid (12 mg, 93.0 %).
69% With Jones reagent; In acetone; at 0℃; for 0.5h; Jones reagent 8 N (0.3 mmol) was added dropwise to a solutionof compound 7 (0.1 mmol) in acetone (4 mL) in an ice bath. Thesolution was stirred for 30 min when TLC analysis showed the totalconsumption of the starting material. The solution was diluted inacetone (15 mL) filtered through celite and evapored under vacuum.The crude extract was purified by flash column chromatographyon silica (hexane:ethyl acetate 3:7) affording compound 23 as a white solid. Yield: 69%. Mp: 155.0-57.4 C. 1H NMR (300 MHz,CDCl3): delta = 7.78-7.90 (m, 2H, Ar), 7.45-7.55 (m, 3H, Ar), 7.25 (s, 1H,Isoxazole). 13C NMR (75 MHz, CDCl3): delta =166.9, 165.5, 162.3, 134.4,133.0, 132.8, 131.9, 130.7, 111.3. HRMS (ESI-TOF) m/z: [M- H]- Calcdfor C10H6NO3 188.0353; Found 188.0321.
  • 6
  • [ 2039-50-1 ]
  • [ 90924-12-2 ]
  • 7
  • [ 90924-12-2 ]
  • selenous acid bis-(3-phenyl-isoxazol-5-ylmethyl) ester [ No CAS ]
  • 8
  • [ 107-19-7 ]
  • [ 698-16-8 ]
  • [ 90924-12-2 ]
YieldReaction ConditionsOperation in experiment
89% With triethylamine; In dichloromethane; at 50℃; for 2h; To a stirred solution of 7 (10 mg, 0.06 mmol) in dichloromethane (DCM) (0.2 ml) was addedpropargyl alcohol (5 mul, 0.09 mmol) and Et3N (13 mul, 0.09 mmol) at room temperature. Then, themixture was heated to 50 C for 2 h. After the removal of the solvent, the residue was purifiedthrough a silica chromatography column (petroleum ether : EtOAc 3 : 1) to afford the product (8)as white solid (10 mg, 89.0 %).
With (1,10-phenanthroline)bis(triphenylphosphine)copper(I) nitrate; In water; at 65℃;Microwave irradiation; Green chemistry; General procedure: In a round bottomed flask, a mixture of benzaldehyde 1a (0.027 g,0.25 mmol, 1.0 equiv) and NaOH (0.020 g, 0.50 mmol, 2.0 equiv) was added toa solution of hydroxylamine hydrochloride (0.0177 g, 0.25 mmol, 1.0 equiv) containing 5 mL of H2O. The reaction mixture was irradiated under microwave heating at 210W for 5 min at 65 C. The progress of the reaction was monitored by TLC. After completion, N-chlorosuccinimide (0.034 g, 0.25 mmol, 1.0 equiv) was added in small proportions for over 2 min, followed by microwave irradiation at same power for 2 min. After completion, phenylacetylene 3a (0.0255 g, 0.25 mmol, 1.0 equiv) and [Cu(phen)(PPh3)2]NO3 catalysts (0.0042 g, 2 mol%) was immediately added to the reaction mixture. Subsequently, the reaction mixture was irradiated under microwave for 5 min. The reaction progress was monitored by TLC. After completion, the reaction mixture was cooled to room temperature and extracted with ethyl acetate (10 mL, twice). The combined organic layer was dried over anhydrous MgSO4. The combined filtrate was subjected to evaporation to obtain the crude compound, which was purified over silica gel column (60 - 120 mesh) using 1% ethyl acetate in hexane as eluent to obtain the corresponding 3,5-diphenylisoxazoles 4a as the product.
With sodium hydrogencarbonate; copper(II) sulfate; sodium L-ascorbate; In water; N,N-dimethyl-formamide; at 30℃; for 0.166667h;Microwave irradiation; General procedure: The compounds were synthesised based on procedure reportedin the literature [38]. For the preparation of the imidoyl chloride, N-chlorosuccinimide (0.1 mmol) was slowly added to a solution of analdoxime (0.105 mmol) in DMF (1 mL) and the reaction was stirreduntil the starting material was not visible on the TLC analysis. After,the reaction was diluted with brine (15 mL), extracted with ethylether (3 x 10 mL), dried over Na2SO4, concentrated under vacuumand utilized without any purification in the next step. Following,propargylic alcohol (0.105 mmol), copper (II) sulphate (2 mol%),sodium ascorbate (10 mol%), sodium bicarbonate (0.4 mmol) and4mL of H2O:t-BuOH were added to the product obtained in the firstpart, and the reaction was further stirred for 4 h. Next, the reactionwas diluted with brine (15 mL), extracted with ethyl acetate(3 x 10 mL), dried over Na2SO4, concentrated under vacuum andthe crude extract was purified by flash column chromatography onsilica (hexane:ethyl acetate 6:4) yielding the expected product.After purification, they were compared via TLC analysis to therespecting compounds synthesized under microwave irradiation,when this comparison was desired, and characterized by NMR andmass spectrometry. 4.1.3. Structural characterization of compounds 6e314.1.3.1. 5-Hydroxymethyl-3-phenylisoxazole (6). Yield: 72%. YieldMW: 77%. Mp: 48.8-49.5 C. 1H NMR (300 MHz, Methanol-d4): delta 7.78-7.85 (m, 2H, Ar), 7.43-7.50 (m, 3H, Ar), 6.76 (s, 1H, Isoxazole),4.71 (s, 2H, CH2). 13C NMR (75 MHz, Methanol-d4):delta 171.7, 162.5, 130.1, 128.9, 128.8, 126.8, 100.0, 56.7. HRMS (ESITOF)m/z: [M+H]+ Calcd for C10H10NO2 176.0712; Found 176.0699
27.36 mg With sodium hydrogencarbonate; copper(II) sulfate; sodium L-ascorbate; at 35℃; for 0.166667h;Microwave irradiation; Sealed tube; General procedure: Under microwave irradiation, to a solution of oxime (1.03 mmol) inDMF (0.3 mL), was added NCS (1.1 mmol) and the mixture was irradiatedin a sealed tube during 1 min, at 35 C and 150 W. After that,propargylic alcohol (1.1 mmol), CuSO4 (0.01 mmol) dilute in 50.0 muL ofwater, sodium ascorbate (0.10 mmol) and NaHCO3 (4.10 mmol) wereadded to the tube. The reaction was irradiated again during 10 min., inthe same conditions above. When reaction time was over, the mixturewas diluted in EtOAc (20.0 mL) and washed with NaCl (2×20.0 mL).The organic phase was dried with anhydrous Na2SO4 and the solventwas removed under reduced pressure yielding the expected product.

  • 9
  • [ 122531-07-1 ]
  • [ 90924-12-2 ]
  • 11
  • [ 107-19-7 ]
  • [ 934-16-7 ]
  • bromo-tris-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)silane [ No CAS ]
  • [ 90924-12-2 ]
  • 12
  • [ 107-19-7 ]
  • [ 934-16-7 ]
  • [ 90924-12-2 ]
YieldReaction ConditionsOperation in experiment
75% With sodium chloride; triethylamine; In tetrahydrofuran; water; Reference Example 68 Triethylamine (7.28 ml) was added to a solution of alpha-chlorobenzaldehyde oxime (4.04 g) and 2-propyn-1-ol (1.66 ml) in tetrahydrofuran (130 ml) and stirred at room temperature for 4 days. Water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The remaining crystals were recrystallized from ethyl acetate-hexane to obtain (3-phenyl-5-isoxazolyl)methanol (3.42 g, yield 75%) as colorless crystals. m.p. 48-49 C.
YieldReaction ConditionsOperation in experiment
General procedure: Production Example 17 {3-[4-(Trifluoromethoxy)phenyl]-1,2-oxazol-5-yl}methanol(2) N-Chlorosuccinimide (1.5 g) was added to a solution of N-hydroxy-1-[4-(trifluoromethoxy)phenyl]methaneimine (2.5 g) in chloroform (50 mL) and the mixture was stirred at room temperature for 1 hr. Propargylalcohol (0.8 mL) was added thereto, triethylamine (1.8 mL) was then added slowly, and the mixture was stirred at room temperature overnight. The solvent was distilled off under reduced pressure, and the resulting residue was then purified by column chromatography (silica gel cartridge, hexane:ethyl acetate=94:6-50:50) to afford the title compound (1.3 g). 1H NMR (200 MHz, CHLOROFORM-d) d ppm 4.81-4.88 (m, 2H), 6.54-6.58 (m, 1H), 7.27-7.37 (m, 2H), 7.79-7.89 (m, 2H)
  • 15
  • 3-phenyl-5-(polyethylene glycol-OCOCH2CH2COOCH2)isoxazole [ No CAS ]
  • [ 90924-12-2 ]
  • 17
  • [ 100-52-7 ]
  • (C5H5)2(Cl)Zr{trans-CH=CH[CH2]4OSi(CH3)2(t-Bu)} [ No CAS ]
  • [ 90924-12-2 ]
  • 20
  • [ 90924-12-2 ]
  • [ 101444-99-9 ]
  • 21
  • [ 135335-38-5 ]
  • [ 90924-12-2 ]
  • 22
  • [ 90924-12-2 ]
  • [ 1011-37-6 ]
YieldReaction ConditionsOperation in experiment
86% With thionyl chloride; sodium chloride; In water; toluene; Reference Example 70 Thionyl chloride (2.41 ml) was added to a solution of (3-phenyl-5-isoxazolyl)methanol (2.89 g) in toluene (10 ml) and stirred at 60 C. for 1 hour. Water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The remaining crystals were recrystallized from ethyl acetate-hexane to obtain 5-(chloromethyl)-3-phenylisoxazole (2.75 g, yield 86%) as pale-brown crystals. m.p. 69-70 C.
With thionyl chloride; In dichloromethane; at 20℃;Inert atmosphere; General procedure: To a stirred solution of ?a? derivatives in freshly distilled CH2Cl2 under N2 atmosphere, at roomtemperature, thionyl chloride (1.5 eq) was added. The reactions were monitored by TLC and, at thetotal consumption of the starting material, they were quenched with cold water and extracted withCH2Cl2. Next, the crude products were solubilized in DMF followed by addition of sodium azide (1.5eq). The reactions were kept at room temperature until TLC analyses indicated the disappearance ofthe starting material, then, they were quenched with water and extracted with EtOAc. In the last step,the crude azide derivatives were solubilized in THF followed by addition of triphenylphosphine (1.5 eq).The reactions were maintained overnight at room temperature, quenched by addition of aqueousNa2CO3 [5% (m/v)] and extracted with EtOAc. The crude amine derivatives (compound d) were usedfor the synthesis of the isoxazolyl-sulfonamide derivatives 1-20 without any further purification.
  • 23
  • [ 90924-12-2 ]
  • [ 1189021-65-5 ]
  • 24
  • [ 90924-12-2 ]
  • [ 72418-40-7 ]
YieldReaction ConditionsOperation in experiment
81% With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; iodine; sodium hydrogencarbonate; In ethanol; water; benzene; at 20℃; for 9h; General procedure: 3-Substituted isoxazole-5-carbaldehydes were synthesized according to reported procedures.37 (3-Phhenylisoxazol-5-yl)methanols (5.0 mmol) were dissolved into benzene (10 mL). An aqueous solution of sodium bicarbonate (13 mL, 1.2 mol/L) was added into the benzene slurry at room temperature. Then, the mixed solid TEMPO (0.5 mmol) was added and solid iodine (10 mmol) dissolved in alcohol was added into the reaction mixture. The reaction mixture was then aged for 10-12 h at room temperature; the reaction was monitored by TLC. The crude product was diluted with ethyl acetate (15 mL). The batch was washed with Na2S2O3 and transferred to a separatory funnel, and the aqueous layer was extracted with ethyl acetate (210 mL). The organic layers were mixed and dried over anhydrous sodium sulfate for 30 min, filtrated and evaporated under vacuum to give the crude product which was purified by column chromatography (silica gel, 200e300 mesh) using petroleum ether/ethyl acetate(4r5: 1) to furnish the product. The yields of obtained 3-substituted isoxazole-5-carbaldehydes products were 58-92%.
With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione; In ethyl acetate;Reflux; A solution of (3-phenylisoxazol-5-yl)methanol (10.0 g) and 2-iodoxybenzoic acid (24.0 g) in ethyl acetate (350 mL) was refluxed overnight. The mixture was cooled to room temperature, filtered and concentrated. The resulting solids were triturated (hexane: diethyl ether = 1: 1) to obtain the title compound (8.22 g) having the following physical data. 1H NMR (DMSO-de): delta 9.97 (s, IH), 8.06-7.91 (m, 3H), 7.64-7.47 (m, 3H).
With Jones reagent; In acetone; at 0℃; for 0.583333h; General procedure: (3-Arylisoxazol-5-yl)methanol 118,19 ( 4 mmol) was taken in dry acetone and cool to 0 oC and added the Jones reagent (CrO3+H2SO4+Acetone) (4 mmol) slowly over 15 minutes. The reaction mixture was stirred for 20 minutes at 0 oC. After completion of reaction, the reaction mixture was filtered through the short pad of celite, collected the filtrate, and concentrated under vacuum. The residue was purified by passing through a column packed with silica gel using petroleum ether/EtOAc (8:2) as eluents.
  • 25
  • [ 1313396-26-7 ]
  • [ 90924-12-2 ]
  • 26
  • [ 1313396-15-4 ]
  • [ 90924-12-2 ]
YieldReaction ConditionsOperation in experiment
65% With silver tetrafluoroborate; phenol; In tetrahydrofuran; for 1h;Reflux; General procedure: To a solution of alkynyl oxime ether 1 (0.15 mmol) in THF (5 mL) were added phenol (28 mg, 0.3 mmol) and AgBF4 (5.8 mg, 0.03 mmol), with a drying tube filled with silica gel at room temperature. After being stirred at reflux for 1-12 h (TLC monitoring), the reaction mixture was concentrated under reduced pressure. The residue was purified by preparative TLC (hexane/AcOEt=3-10:1) to afford isoxazole 3. The physical and spectroscopic data of 3a5 and 3j12h were in accord with those reported in the literature.
  • 27
  • [ 13829-77-1 ]
  • [ 90924-12-2 ]
  • 28
  • 1-phenyl-2-propyn-1-one O-(phenylmethyl)oxime [ No CAS ]
  • [ 90924-12-2 ]
  • 29
  • [ 90924-12-2 ]
  • 2-[N-(benzyloxy)formamido]methyl}-N-[(3-phenylisoxazol-5-yl)methyl]hexanamide [ No CAS ]
  • 30
  • [ 90924-12-2 ]
  • N-(4-amino-2-oxo-4-phenylbutyl)-2-[(N-hydroxyformamide)methyl]hexanamide [ No CAS ]
  • 33
  • [ 107-19-7 ]
  • [ 932-90-1 ]
  • [ 90924-12-2 ]
YieldReaction ConditionsOperation in experiment
76.8% (2) 3-phenyl-5-hydroxymethyl-isoxazole10.0 mmol of benzaldehyde oxime and30 mL of dry dichloromethane were placed in a 250 mL single-necked roundEP2 752 413 A18510152025303540455055bottom flask. 1.60g (12.0 mmol) of N-chlorosuccinimide (NCS) was added under stirring. After NCS was completelydissolved by slightly heating, 0.56g (10.0 mmol) of 2-propyn-1-ol was added dropwise, and then 20 mL solution of10.1g (10.0 mmol) of triethylamine in dichloromethane. After the addition was complete, the system was refluxed.After the completion of the reaction monitored by TLC, the mother liquor was washed with water, dried over anhydroussodium sulfate, and seperated by column chromatography (Vpetroleum ether: Vethyl acetate = 5:1 - 2:1) to give 3-phenyl-5-hydroxymethyl- isoxazole in 76.8% yield.(3) 3-phenyl-5-aminomethyl-isoxazole
76.8% With N-chloro-succinimide; triethylamine; In dichloromethane;Reflux; 10.0 mmol of benzaldehyde oxime and 30 mL of dry dichloromethane were placed in a 250 mL single-necked round-bottom flask. 1.60 g (12.0 mmol) of N-chlorosuccinimide (NCS) was added under stirring. After NCS was completely dissolved by slightly heating, 0.56 g (10.0 mmol) of 2-propyn-1-ol was added dropwise, and then 20 mL solution of 10.1 g (10.0 mmol) of triethylamine in dichloromethane. After the addition was complete, the system was refluxed. After the completion of the reaction monitored by TLC, the mother liquor was washed with water, dried over anhydrous sodium sulfate, and separated by column chromatography (Vpetroleum ether:Vethyl acetate=5:1-2:1) to give 3-phenyl-5-hydroxymethyl-isoxazole in 76.8% yield.
76.8% With N-chloro-succinimide; triethylamine; In dichloromethane; at 0℃;Reflux; The benzaldehyde oxime 10.0mmol dry dichloromethane was added 30mL and 250mL single-necked round-bottomed flask was added with stirring 1.60g (12.0mmol) N- chlorosuccinimide (NCS), heating slightly to dissolve all the NCS, was added dropwise 0.56g (10.0mmol) 2- propynyl-1-ol, followed by the slow dropwise added 20mL dichloromethane solution containing 10.1g (10.0mmol) of triethylamine, and refluxed after addition. After TLC detection, the mother liquor was washed with water, dried over anhydrous sodium sulfate and separated by column chromatography (V: petroleum ether: V ethyl acetate 5: 1-2: 1) to give 3-phenyl-5-hydroxymethylisoxazole , Yield 76.8%.
76.8% With N-chloro-succinimide; triethylamine; In dichloromethane; at 0℃;Reflux; 10.0 mmol of formaldoxime and 30 mL of dry dichloromethane were added to a 250 mL single-neck round bottom flask, 1.60 g (1.0 mmol) of N-chlorosuccinimide (NCS) was added with stirring, after slightly heating until all the NCS was dissolved, 0.56 g (10.0 mmol) of 2-propyn-1-ol was added dropwise, soon afterwards, 20 mL of a dichloromethane solution containing 10.1 g (10.0 mmol) of triethylamine was slowly added dropwise. After the addition, the system was refluxed. After tlc detection reaction is completed, the mother liquid washing, dried over anhydrous sodium sulfate, and separated by column (V petroleum ether: V ethyl acetate 5:1~2:1) to obtain 3-phenyl-5-hydroxymethyl-isoxazole, yield 76.8 %.
With N-chloro-succinimide; triethylamine; In dichloromethane; at 0℃;Reflux; (2) Synthesis of 3-phenyl-5-hydroxymethyl-isoxazole 10.0 mmol of Benzaldehyde oxime and 30 ml of dry dichloromethane were added into a 250 ml single-necked round-bottom flask. After the addition of 1.60g (12.0 mmol) of N-chlorosuccinimide (NCS) under stirring, the mixture was slightly heated until NCS was completely dissolved. 0.56g (10.0 mmol) of 2-propyn-1-ol was added dropwise, and then 20 ml solution of triethylamine in dichloromethane containing 10.1g (10.0 mmol) of triethylamine was slowly added dropwise. After the addition was complete, the system was refluxed. After the completion of the reaction monitored by TLC, the mother liquor was washed with water, dried over anhydrous sodium sulfate and was separated on column (Vpetroleum ether: Vethylacetate = 5:1 - 2:1) to give 3-phenyl-5-hydroxymethyl-isoxazole in 76.8% yield.
General procedure: To a solution of aldoximes (20 mmol) in N,N-dimethylformamide (DMF; 15 mL), N-chlorosuccinimide (NCS; 20.2 mmol, 2.7 g) was added under glacial bath conditions. Triethylamine (1.5 mmol, 4.17 mL)was added to the reaction solution followed by propargyl alcohol (60 mmol, 3.5 mL). The mixture was stirred at ambient temperature until the reaction was complete as monitored by TLC monitoring (ethyl acetate/petroleum ether = 1 : 2). Following the reaction, the slurry was extracted with ethyl acetate.The organic layers were dried over anhydrous sodium sulphate, filtered and then evaporated under vacuum to provide the crude product which was purified by column chromatography (silica gel, 200-300 mesh; Merck, Germany) to furnish the product with a 44-62 % yield.
With N-chloro-succinimide; triethylamine; In dichloromethane;Reflux; The 10.0 mmol benzaldehyde oxime waning and 30mL of dry dichloromethane was added 250mL single burning mouth round bottom flask was added with stirring 1.60g (12.0mmol) N- chlorosuccinimide (NCS), slightly heated to dissolve all NCS after the dropwise addition of 0.56g (10.0mmol) 2- propynyl-1-ol, followed by the slow dropwise 20 mL of methylene chloride solution containing 10.18 (10.0 mmol) of triethylamine was added after completion of the reaction was refluxed for detecting .tlc after the mother liquor washed with water, dried over anhydrous sodium sulfate, column separation (V petroleum ether: V ethyl acetate 5:1-2:1) to give 3-phenyl-5-hydroxymethylisoxazole, yield 76.8%
General procedure: A mixture of a' (10.0 mmol) in CH2Cl2 was stirred at room temperature, NCS (1.60 g, 12.0 mmol) was then added. The resulted mixture was stirred at reflux and propynol (0.56 g, 10.0 mmol) was added dropwise. After 0.5 h, triethylamine (1.01 g, 10 mmol) was added dropwise and refluxed for another 4 h. After cooling, the reaction mixture was washed with water and evaporated under reduced pressure. The obtained residue was purified by silica gel chromatography with petroleum ether/ethyl acetate as eluent to give intermediate b'.
With N-chloro-succinimide; triethylamine; In dichloromethane;Reflux; Add 10.0 mmol of benzaldehyde oxime and 30 mL of dry dichloromethane to a 250 mL single-neck round bottom flask.1.60 g (12.0 mmol) of N-chlorosuccinimide (NCS) was added with stirring.After slightly heating until the NCS is completely dissolved,0.56 g (10.0 mmol) of 2-propyn-1-ol was added dropwise.Then 20 mL of a dichloromethane solution containing 10.1 g (10.0 mmol) of triethylamine was slowly added dropwise.After the addition, the system is refluxed. After the TLC detection reaction is completed,The mother liquor is washed,Dry over anhydrous sodium sulfate,Column separation (V petroleum ether: V ethyl acetate 5:1 ~ 2:1)That is, 3-phenyl-5-hydroxymethyl-isoxazole was obtained in a yield of 76.8%.

  • 34
  • [ 90924-12-2 ]
  • C15H19NO4S [ No CAS ]
  • 35
  • [ 90924-12-2 ]
  • C14H16N4O [ No CAS ]
 

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