[ CAS No. 546-88-3 ] {[proInfo.proName]}

Name: 546-88-3|Acetohydroxamic acid|98%
Brand: Ambeed
SKU: A168949
Price: 5.0 USD
Availability: InStock
Rating: 98 (32 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

HazMat Fee +

There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

2D 3D

Structure of 546-88-3 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 546-88-3 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 546-88-3 ]

SDS Specification

Alternatived Products of [ 546-88-3 ]

Product Details of [ 546-88-3 ]

CAS No. :	546-88-3	MDL No. :	MFCD00009994
Formula :	C₂H₅NO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	RRUDCFGSUDOHDG-UHFFFAOYSA-N
M.W :	75.07	Pubchem ID :	1990
Synonyms :	N-Hydroxyacetamide;AHA;NSC 408425;NSC 176136;NSC 5073

Calculated chemistry of [ 546-88-3 ]

Physicochemical Properties

Num. heavy atoms :	5
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.5
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	2.0
Molar Refractivity :	15.46
TPSA :	49.33 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.89 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.63
Log Po/w (XLOGP3) :	-1.59
Log Po/w (WLOGP) :	-0.49
Log Po/w (MLOGP) :	-0.96
Log Po/w (SILICOS-IT) :	-0.98
Consensus Log Po/w :	-0.68

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	0.76
Solubility :	434.0 mg/ml ; 5.78 mol/l
Class :	Highly soluble
Log S (Ali) :	1.06
Solubility :	867.0 mg/ml ; 11.6 mol/l
Class :	Highly soluble
Log S (SILICOS-IT) :	0.44
Solubility :	206.0 mg/ml ; 2.75 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.3

Safety of [ 546-88-3 ]

Signal Word:	Danger	Class:	N/A
Precautionary Statements:	P501-P202-P201-P280-P308+P313-P405	UN#:	N/A
Hazard Statements:	H360	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 546-88-3 ]

* 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 [ 546-88-3 ]
Downstream synthetic route of [ 546-88-3 ]

[ 546-88-3 ] Synthesis Path-Upstream 1~12

1
[ 546-88-3 ]
[ 394-47-8 ]
[ 36216-80-5 ]

Yield	Reaction Conditions	Operation in experiment
53.7%	With potassium carbonate In N,N-dimethyl-formamide at 80℃;	2- fluorobenzonitrile (6.1g, 50.0mmol), acetohydroxamic acid (5.6g, 75.0mmol) and potassium carbonate (10.4g, 75mmol) was dissolved in DMF (40mL), the mixture was stirred overnight and heated to 80 .With ethyl acetate (100mL × 2) and extracted.The combined organic phases were washed with water (100 mL × 2), saturated brine (100 mL), dried over anhydrous sodium sulfate.Filtered, and the solvent was evaporated under reduced pressure and the crude product purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 4/1), as a white solid (3.6g, 53.7percent).

Reference： [1] Tetrahedron Letters, 1996, vol. 37, # 17, p. 2885 - 2886
[2] Patent: CN104530046, 2016, B, . Location in patent: Paragraph 0202; 0203; 0204; 0205

2
[ 34662-32-3 ]
[ 546-88-3 ]
[ 89692-53-5 ]

Yield	Reaction Conditions	Operation in experiment
66%	Stage #1: With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃; for 0.5 h; Stage #2: for 4.5 h;	To a solution of N-hydroxyacetamide (3.1 g, 41 mmol) in dry N,N-dimethylformamide (60 mL) at room temperature was added potassium t-butoxide (4.6 g, 41 mmol). After stirring for 30 minutes, 4-chloro-2-nitrobenzonitrile (5.0 g, 27 mmol) was added, and stirring was continued for another 4.5 hours. On completion, the reaction mixture was poured into a mixture of brine (60 mL) and ethyl acetate (60 mL). The organic phase was separated, dried over anhydrous sodium sulfate, filtered and concentrated to dryness. The residue was purified by silica gel chromatography [petroleum ether: ethyl acetate = 3:11 to afford compound B-l (3.1 g, 66percent yield) as a pale yellow solid. ‘H-NMR (DM50-cl6, 400 MHz): 7.84-7.82 (d, J=8.8 Hz, 1H), 7.65-7.64 (d, J=1.2 Hz, 1H), 7.33-7.3 1 (dd, J=1.2 Hz, J=8.8 Hz, 1H), 6.52 (s, 2H).

Reference： [1] Patent: WO2017/27600, 2017, A1, . Location in patent: Paragraph 00256; 00257
[2] Tetrahedron Letters, 1996, vol. 37, # 17, p. 2885 - 2886

3
[ 546-88-3 ]
[ 179232-29-2 ]
[ 65685-51-0 ]

Yield	Reaction Conditions	Operation in experiment
31%	Stage #1: With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide for 0.5 h; Stage #2: at 20℃; for 240 h;	Step A: 6-bromobenzo[d]isoxazol-3-ol: N-hydroxyacetamide (0.99 g, 12.9 mmol) was dissolved in DMF (20 mL). To this was added KOt-Bu (1.44 g, 12.9 mmol) and the reaction was stirred for 30 minutes before addition of methyl 4-bromo-2-fluorobenzoate (2.0 g, 8.58 mmol). The reaction mixture was stirred at ambient temperature for 10 days, then diluted with ethyl acetate (50 mL) and 1N NaOH (50 mL). The aqueous layer was washed with ethyl acetate, then acidified with 2N HCl (30 mL). The desired product was collected by filtration (570 mg, 31percent).

Reference： [1] Patent: US2007/49603, 2007, A1, . Location in patent: Page/Page column 62

4
[ 64-17-5 ]
[ 542-10-9 ]
[ 7803-49-8 ]
[ 107-29-9 ]
[ 546-88-3 ]
[ 22606-42-4 ]

Reference： [1] Journal of the American Chemical Society, 1941, vol. 63, p. 2202

5
[ 546-88-3 ]
[ 38180-46-0 ]
[ 114080-93-2 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 24, p. 7357 - 7362

6
[ 546-88-3 ]
[ 97509-75-6 ]
[ 114080-93-2 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 14, p. 3142 - 3145
[2] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 14, p. 3142 - 3145

7
[ 6602-54-6 ]
[ 546-88-3 ]
[ 92914-74-4 ]

Yield	Reaction Conditions	Operation in experiment
48%	Stage #1: With potassium <i>tert</i>-butylate In 1,2-dimethoxyethane at 20℃; for 2 h; Inert atmosphere Stage #2: at 20℃; for 25 h; Inert atmosphere	Method 1. Representative example Isoxazolo[5,4-b]pyridin-3-amine (2) From 2-chloronicotinonitrile in 1,2-dimethoxyethane in 48percent yield

Reference： [1] Patent: WO2016/24233, 2016, A1, . Location in patent: Page/Page column 33

8
[ 546-88-3 ]
[ 3939-13-7 ]
[ 92914-74-4 ]

Yield	Reaction Conditions	Operation in experiment
28%	Stage #1: With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃; for 0.5 h; Stage #2: at 50℃; for 5 h;	Synthesis of intermediate VX001: Isoxazolo[5,4-b]pyridin-3-amine 909 mg (8.1 mmol) of KO-t-Bu were added, with vigorous stirring, to a suspension of 668 mg (8.9 mmol) of acethydroxamic acid in DMF (20 ml), and the mixture was stirred for 30 min at RT. 990 mg (8.1 mmol) of 2-fluoro-nicotinonitrile were then added, and stirring was carried out for a further 5 h at 50° C. The mixture was then extracted with EA and the organic phase was dried over Na₂SO₄, filtered and concentrated in vacuo. CC (hexane/EA 7:3) of the residue yielded 305 mg (2.3 mmol, 28percent) of isoxazolo[5,4-b]pyridin-3-amine.

Reference： [1] Patent: US2010/234419, 2010, A1, . Location in patent: Page/Page column 15

9
[ 546-88-3 ]
[ 68325-15-5 ]
[ 114080-94-3 ]

Yield	Reaction Conditions	Operation in experiment
41%	With potassium carbonate In N,N-dimethyl-formamide at 20℃;	Intermediate 1 : lsoxazolo[5,4-cipyridin-3-ylamine.; To a solution of 3-chloro-isonicotinitrile (1.13 g, 8.36 mmol) in DMF (6.0 mL) were added potassium carbonate (1.69 g, 12.2 mmol) and acetohydroxamic acid (0.91 g, 12.2 mmol). The reaction mixture was stirred at rt overnight, diluted with EtOAc (200 mL) and extracted with saturated aqueous NaHCO₃ (200 mL) then saturated aqueous NaCI (100 mL). The aqueous layers were back extracted with EtOAc (200 mL) and the combined organic layers were dried (MgSO₄) and concentrated. The crude residue was purified (FCC, 2 N NH₃ in MeOH/DCM) to give isoxazolo[5,4-c]pyhdin-3-ylamine (0.447 g, 41 percent). MS (ESI⁺): calcd for C₆H₅N₃O m/z 135.04, found 136.2 (M+H)⁺. ¹H NMR (d₆-DMSO): 8.93 (d, J = 0.8, 1 H), 8.45 (d, J = 5.2, 1 H), 7.88-7.86 (dd, J = 5.2, 1.2, 1 H), 6.72 (br s, 2H).

Reference： [1] Patent: WO2010/68452, 2010, A1, . Location in patent: Page/Page column 26
[2] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 24, p. 7357 - 7362

10
[ 546-88-3 ]
[ 105942-08-3 ]
[ 177995-39-0 ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide for 0.5 h; Stage #2: at 20℃; for 2 h;	Step A: 6-Bromobenzo[d]isoxazol-3-amine: N-hydroxyacetamide (1.13 g, 15.0 mmol) was dissolved in DMF (20 mL). To this was added KOt-Bu (1.68 g, 15.0 mmol) and the reaction was stirred for 30 minutes before addition of 4-bromo-2-fluorobenzonitrile (2.0 g, 10.0 mmol). The reaction mixture was left at ambient temperature for 2 hours, then diluted with ethyl acetate (50 mL) and water (50 mL). The aqueous layer was extracted with ethyl acetate The combined organics were washed with water, dried, filtered and concentrated. The crude product was purified by flash column chromatography, eluting with ethyl acetate/hexanes (1:4), ethyl acetate/hexanes (1:3) to give the desired product (1.35 g, 63percent). MS (APCI) m/z 215.2, 217.1 (M+1).

Reference： [1] Tetrahedron Letters, 1996, vol. 37, # 17, p. 2885 - 2886
[2] Patent: US2007/49603, 2007, A1, . Location in patent: Page/Page column 61-62
[3] Patent: WO2010/51042, 2010, A1, . Location in patent: Page/Page column 135
[4] Patent: WO2014/151147, 2014, A1, . Location in patent: Paragraph 00502
[5] Patent: US2014/357651, 2014, A1, . Location in patent: Paragraph 0485
[6] Patent: US9174994, 2015, B2, . Location in patent: Page/Page column 118

11
[ 546-88-3 ]
[ 179897-89-3 ]
[ 177995-39-0 ]

Reference： [1] Patent: US9174994, 2015, B2, . Location in patent: Page/Page column 117

12
[ 546-88-3 ]
[ 179897-89-3 ]
[ 455280-00-9 ]

Yield	Reaction Conditions	Operation in experiment
62%	Stage #1: With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 30℃; Stage #3: With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide	The title compound was prepared by a modification of the literature procedure as described in Palermo, M. G., Tetrahedron Lett, 37:2885 (1996). A single neck 50 mL flask equipped with a magnetic stirred was charged with N-hydroxyacetamide (2.63 g, 35.0 mmol) and DMF (100 mL). Then, KOtBu (3.93 g, 35.0 mmol) was added in one portion. The temperature rose to 30⁰C. The mixture was stirred for Ih and, 5-bromo~2-fluorobenzonitrile (7 g, 35.0 mmol) was added. The reaction mixture was stirred for overnight. A further portion of KOtBu (1.96 g, 17.5mmo) was added and the solution was again stirred overnight. The mixture was poured into brine and CH2CI2 and the layers were separated. The organic phase was dried (Na₂SO₄) and concentrated in vacuo. The residue was purified by flash column chromatography (BIOTAGE.(R)., eluting with a gradient of 0 to 40percent EtOAc in hexanes) to afford the title compound (4.59 g, 62percent) as a colorless solid. ¹H NMR (500 MHz, DMSOd₆) δ 8.09 (d, J = 1.8 HZ, IH), 7.65 (dd, J = 2.1, 8.9 Hz, IH), 7.45 (d, J = 8.9 Hz₅ IH), 6.49 (s, 2H). LCMS: Anal. Calcd. for C₇H₅BrN₂O: 211₅ 213; found: 212, 214 (M+H)⁺.

Reference： [1] Patent: WO2010/138488, 2010, A1, . Location in patent: Page/Page column 57-58
[2] Patent: WO2010/51042, 2010, A1, . Location in patent: Page/Page column 134
[3] Patent: WO2014/151147, 2014, A1, . Location in patent: Paragraph 00502
[4] Patent: US2014/357651, 2014, A1, . Location in patent: Paragraph 0485

[ 546-88-3 ] Synthesis Path-Downstream 1~88

1
[ 108-24-7 ]
[ 546-88-3 ]

Yield	Reaction Conditions	Operation in experiment
55%	With hydroxylamine monohydrate In water at 20 - 80℃;	To a stirred 50% solution of hydroxylamine hydrate (25 ml, 0.42 mole) and 25 ml of waterin a beaker stirred using magnetic stir bar, was added dropwise 45ml (49.3g, 0.42 mol) ofacetic anhydride; the temperature of reaction mixture rose to 80o during the addition. Afterthe addition of acetic anhydride was complete, the clear liquid obtained was allowed to coolto room temperature with continued stirring. The reaction mixture was then extracted withethyl acetate (4 × 70 mL). The combined extracts were concentrated in vacuo to a volumeof 90 mL and cooled to 0C for 16 hrs. The resulting precipitate (20.0 g, 88% pure) wascollected and recrystallized from acetone to give 17.0 g. (55%) of 98% AHA as a colorlesssolid, mp. 86-88C, lit.18 88-89C.
	With hydroxylamine hydrochloride
	With hydroxylamine hydrochloride

Reference： [1]Sukumar; Rao, R.V. Subba; Natarajan [Organic Preparations and Procedures International, 2014, vol. 46, # 1, p. 85 - 87]
[2]Miolati [Chemische Berichte, 1892, vol. 25, p. 700]
[3]Hoare; Olson; Koshland Jr. [Journal of the American Chemical Society, 1968, vol. 90, # 6, p. 1638 - 1643]

2
[ 141-78-6 ]
[ 546-88-3 ]

Yield	Reaction Conditions	Operation in experiment
97.1%	With hydroxylammonium sulphate; potassium etoxide In ethanol at 25℃; for 2h;	2 To the reactor was added 16.4 g (0.1 mol) of hydroxylamine sulfate, 68.0 g of an ethanol solution of 20% sodium ethoxide was added dropwise at room temperature, and the molar ratio of sodium ethoxide to hydroxylamine sulfate was 2: 1 and stirred for about 0.5 hours. (0.1 mol) of ethyl acetate was added dropwise. After about 1 h, the reaction was carried out for 1 hour. The reaction temperature was maintained at 25 ° C. After completion of the reaction, the reaction was continued until the concentrated sulfuric acid was added to the final pH = 6, filtered, concentrated, concentrated solution about 10ml, mixed with chloroform and ethanol 60ml, the volume ratio of 9: 1 crystallization, needle-like crystal acetohydroxamic acid 14.6g, the yield of 97.1%.
84.6%	With hydroxyamino hydrochloride; sodium hydroxide In methanol; lithium hydroxide monohydrate at 40℃; for 3h; Large scale;	1.1-1.9; 1-5 1) Add 2.6L of methanol and 1300g of hydroxylamine hydrochloride to the three-necked reaction flask (10L), place the reaction flask in an ice-water bath, and keep stirring;2) Dissolve 748g of sodium hydroxide in 1.3L of water, and then pour the sodium hydroxide solution into the reaction bottle to neutralize hydrochloric acid;3) Will 1978gEthyl acetate was added to the reaction flask, the temperature of the reaction system was raised to 40 ° C, and stirring was continued for 1 h;4) Dissolve the remaining 748g of sodium hydroxide in 1.3L of water, add it to the reaction flask at 40 ° C, and continue the reaction at this temperature for 2h;5) The reaction solution was concentrated on a rotary evaporator to remove methanol;6) In an ice-water bath, adjust the reaction system to pH = 4-5 with concentrated hydrochloric acid;7) Evaporate the water in the reaction system to dryness;8) Add a total of 6.5L of ethyl acetate to the reaction system, heat and extract 5 times, and then concentrate the extract to 2L;9) Add 10 ml of acetone to the concentrate, stir at low temperature for 30 min at 0 ° C, filter to obtain a white solid, and dry at 40 ° C to obtain 1000 g of the product. The calculated yield is 84.6%.During the reaction, ultraviolet light was used to track the progress of the reaction. The purity of the compound was detected by liquid chromatography. From the test results, the purity of the product was 98.0%. The structure of the product was confirmed by nuclear magnetic resonance and carbon spectrum. As shown in Fig. 1, it was confirmed that the obtained product was acetoxyhydroxamic acid.
	With hydroxylamine; potassium etoxide

	With sodium hydroxide; hydroxylamine
	With methanol; hydroxylamine
	With potassium hydroxide; hydroxyamino hydrochloride In methanol for 5h; temp. < 30 deg C;
	With hydroxylamine Ambient temperature;
	With hydroxylamine In aq. buffer at 40℃; for 1.75h; Micellar solution; Enzymatic reaction;	2.3.1. Acyltransferase activity assay of immobilized P. aeruginosa cells in the reverse micellar system General procedure: The activity assays in the reverse micellar medium were performed using intact cells from P. aeruginosa L10 strain containing amidase and according to a methodology previously described [3], in a thermostatic water bath at 40°C. Briefly, the acyltransferase activity was investigated in a 5mL stirred reverse micellar system of 200mM TTAB in heptane/octanol (80/20%, v/v) containing P. aeruginosa cells (0.050g cells/mL in 10mM HEPES buffer at pH 7.2), hydroxylamine solution (freshly neutralized to pH 7). The water content in the system, usually defined through the parameter w0=[H2O]/[surfactant], was controlled by adjusting the added volume of buffer 10mM HEPES at pH 7.2 and established to a value of 10. The amide or ester substrate solution in 10mM HEPES buffer at pH 7.2 was injected in order to initiate the reaction. The rate of reaction was determined by following the increase in the concentration of the reaction product a, hydroxamic acid derivative, during the course of the reaction as described in [3]. Calibration curves with acetohydroxamate, benzohydroxamate, butyrylhydroxamate, glycine hydroxamate and alanine hydroxamate were established and values for the extinction coefficient (ε) were obtained of 0.105mM-1 (R2=0.993), 0.1210mM-1 (R2=0.964), 0.038mM-1 (R2=0.993), 0.0072mM-1 (R2=0.965), 0.0057mM-1 (R2=0.972), respectively. One enzyme unit (U) is defined as the amount of enzyme required to produce 1 μmol of hydroxamic acid derivative per min under these experimental conditions.
	With hydroxyamino hydrochloride; sodium hydroxide In lithium hydroxide monohydrate Cooling with ice;	2 Example 2 (E)-Glutazol-4-ene-3β-mercapto-methyl-6-one (Compound 3) and (E)-Glutosyl-3β,6β-mercapto-methyl-4-ene (Compound 4) Hydroxylamine hydrochloride (100.0 mg), ethyl acetate (240 μl),Sodium hydroxide (126.0 mg), dissolved in 500 μl of deionized water,The reaction was carried out under ice bath conditions, and TLC (thin layer silica gel plate) was monitored until the reaction was completed. After completion of the reaction, methyl bromide (114.1 μl) was added and the reaction was carried out in an ice bath.TLC (thin layer silica gel plate) was monitored until the reaction was complete. After the reaction is completed,After extracting by-products with petroleum ether, the lower layer solution is taken.Extract three times with ethyl acetate and take an ethyl acetate layer.The solvent was evaporated to dryness under reduced pressure to yield white crystals,Further, ethanol (10.0 ml) and hydrochloric acid (15 μl) were added, and the reaction was carried out at 65 ° C, and the reaction was completed by TLC (thin layer silica gel).After the reaction is completed,Evaporation of the solvent gave pale yellow crystals of 2:m.p.(81.3 mg, yield is 69.3%)
	With hydroxyamino hydrochloride; sodium hydroxide In lithium hydroxide monohydrate at 0℃; for 4h;	(E)-4-ene-sitosterol-3β-oxime group-methyl-6-one (3) and (E)-sitosterol-3β,6β-hydroxyimino-methyl-4-ene (31). To a 50 mL round bottomflask was added hydroxylamine hydrochloride (100.0 mg), ethyl acetate(240.0 μL), sodium hydroxide (126.0 mg) and pure water (500.0 μL).The reaction was stirred in 0 °C for 4 h. TLC (thin layer of silica gelplate) detected complete reaction. The methyl bromide (114.1 μL) wasadded in the solvent and continue reacted for 2 h at 0 °C. TLC alsodetected complete reaction. After extraction of the by-product withpetroleum ether, the solution was taken out and extracted three timeswith ethyl acetate. The ethyl acetate layer was evaporated and thesolvent was evaporated under reduced pressure to give white crystals ofmethoxycarboxamide. Then add ethanol (10.0 mL), hydrochloric acid(15.0 μL), 65 °C reaction, TLC (thin layer of silica gel plate) to the reactionis complete. After completion of the reaction, the solvent wasevaporated to dryness to give pale yellow crystals of methoxyaminehydrochloride (81.3 mg, yield 69.3%). After that, 2 (50.0 mg), methoxylaminehydrochloride (29.1 mg) and sodium acetate (10.0 mg) wereplaced in a 50 mL round bottom flask and dissolved in 10 mL of ethanolat 45 °C, TLC monitoring to complete reaction. The solvent is evaporatedunder reduced pressure. And the residue was purified by silica gelcolumn chromatography with a Petroleum Ether : EtOAc=10:1 (V/V)gradient to give (E)-4-ene-sitosterol-3β-oxime group-methyl-6-one(23.0 mg, 50.3 mmol, 43.0% yield).
	With hydroxyamino hydrochloride; sodium hydroxide In ethanol; lithium hydroxide monohydrate at 20℃; Cooling with ice;
	With hydroxyamino hydrochloride; sodium hydroxide In lithium hydroxide monohydrate at 0 - 20℃; for 1h;	3.2.2. General Procedure for Synthesis of O-substituted hydroxylamines 3d-3j General procedure: The water (5 mL) mixing hydroxylamine hydrochloride (0.10 mol), ethyl acetate(0.18 mol) and 28% sodium hydroxide aqueous solution (25 mL) were stirred at 0 C.The resultant mixture was then stirred at room temperature for 1 h. After that, halogenated hydrocarbon (0.11 mol) was dropwise added and the reaction was stirred at 60 C for further 6 h. Subsequently, the reaction mixture was extracted with petroleum ether and ethyl acetate. The organic layer was combined and dried by anhydrous sodium sulfate,then the solvent was removed under reduced pressure and oily product was obtained.The obtained oily product was dissolved in ethyl alcohol, and 36% aqueous hydrochloric acid was added to the solution. The mixture was stirred at 50 C for 4 h. Finally, the reactionwas neutralized to pH 7.0 by saturated sodium bicarbonate aqueous solution, and thenextracted with dichloromethane. The extracts were dried over anhydrous sodium sulfate,and concentrated under vacuum to obtain the title compounds 3d-3j
	With ammonia; dihydrogen peroxide In lithium hydroxide monohydrate; <i>tert</i>-butyl alcohol at 60℃; for 4.5h; Molecular sieve;	1-4 Embodiment 1, the synthetic method of acetohydroxamic acid: Taking ethyl acetate (CH3COOC2H5) as the reaction raw material, the selected catalyst is titanium-silicon molecular sieve TS-1, ammonia is liquid ammonia, that is, ammonia water with a mass concentration of 25%, and the solvent is an aqueous solution of tert-butanol with a volume content of 10% of tert-butanol ; That is, the solvent used is a mixed solvent of 10% tert-butanol and 90% water by volume.Specifically, perform the following steps in sequence:1. Method 1 (ammonia is added at one time):1.1), add catalyzer, solvent, reaction raw material and ammonia to the reactor, stir, form reaction system;Described reaction raw material: the weight ratio of catalyst=1:0.1; Reaction raw material: the mol ratio of ammonia=1:1.5;Described reaction raw material: solvent=1g:10g material-liquid ratio.1.2), set reaction temperature to be 60 ;After the reaction system was heated to 60°C, a hydrogen peroxide solution with a mass concentration of 30% was added dropwise for 4 hours, and the reaction was continued for 0.5 hours at a temperature of 60°C after the dropwise addition;Described reaction raw material: the mol ratio of hydrogen peroxide=1:1;2. The reaction product obtained in step 1.2) is filtered to separate out the catalyst, that is, the obtained filter residue is a solid catalyst (returnable to the system for reuse), and the obtained filtrate is a reaction solution containing substances such as hydroxamic acid, solvent, water, and ammonia. The filtrate is subjected to conventional post-treatments such as conventional rectification, evaporation, and crystallization to obtain the product acethydroxamic acid.

Reference： [1]Current Patent Assignee: BEIJING SUNPU BIOCHEMISTRY TECHNOLOGY - CN105152975, 2017, B Location in patent: Paragraph 0043-0044
[2]Current Patent Assignee: CHINESE ACADEMY OF AGRICULTURAL SCIENCES - CN110483336, 2019, A Location in patent: Paragraph 0023-0061
[3]Inoue; Yukawa [Nippon Nogeikagaku Kaishi, 1940, vol. 16, p. 504][Bl.agric.chem.Soc., 1940, vol. 16, p. 100][Chem.Abstr., 1941, p. 730] Inoue; Yukawa [Journal of the Agricultural Chemical Society of Japan, 1940, vol. 16, p. 101][Chem.Abstr., 1941, p. 730,731]
[4]Hantzsch [Chemische Berichte, 1894, vol. 27, p. 804]
[5]Virtanen; Saris [Acta Chemica Scandinavica (1947), 1956, vol. 10, p. 483]
[6]Ruiqin, Wang; Xiaolan, Yu; Zhenye, Feng; Haq, Mian M. I.; Khurshid, Muhammed M. P.; et al. [Journal of the American Chemical Society, 1989, vol. 111, # 1, p. 114 - 120]
[7]Brown, David A.; Glass, William K.; Mageswaran, Rajeswary; Girmay, Berhane [Magnetic Resonance in Chemistry, 1988, vol. 26, p. 970 - 973]
[8]Bernardo, Marisa; Pacheco, Rita; Serralheiro, Maria Luisa M.; Karmali, Amin [Journal of Molecular Catalysis B: Enzymatic, 2013, vol. 93, p. 28 - 33]
[9]Current Patent Assignee: CHINA PHARMACEUTICAL UNIVERSITY - CN106800580, 2019, B Location in patent: Page/Page column 12-30
[10]Cui, Shaoyu; Jiang, Hongli; Chen, Lei; Xu, Jian; Sun, Wenzhuo; Sun, Haopeng; Xie, Zijian; Xu, Yunhui; Yang, Fubai; Liu, Wenyuan; Feng, Feng; Qu, Wei [Bioorganic Chemistry, 2020, vol. 98]
[11]Al Fantazi, Akram; Asatkar, Ashish; Ebenso, Eno E.; Hussain, Chaudhery Mustansar; Khan, Fahmida; Verma, Chandrabhan; Verma, Dakeshwar Kumar [Journal of Molecular Liquids, 2020, vol. 314]
[12]Dai, Peng; Jiao, Jian; Wang, Qing-Qing; Zhang, Shu-Guang; Zhang, Wei-Hua [Molecules, 2021, vol. 26, # 2]
[13]Current Patent Assignee: JIANGSU ECOWAY SCIENCE and TECH CO LTD - CN114105824, 2022, A Location in patent: Paragraph 0067-0096

3
[ 546-88-3 ]
[ 75-31-0 ]
[ 1118-69-0 ]

Reference： [1]Chemical and pharmaceutical bulletin,1983,vol. 31,p. 2130 - 2133

4
[ 34662-32-3 ]
[ 546-88-3 ]
[ 89692-53-5 ]

Yield	Reaction Conditions	Operation in experiment
66%		To a solution of N-hydroxyacetamide (3.1 g, 41 mmol) in dry N,N-dimethylformamide (60 mL) at room temperature was added potassium t-butoxide (4.6 g, 41 mmol). After stirring for 30 minutes, <strong>[34662-32-3]4-chloro-2-nitrobenzonitrile</strong> (5.0 g, 27 mmol) was added, and stirring was continued for another 4.5 hours. On completion, the reaction mixture was poured into a mixture of brine (60 mL) and ethyl acetate (60 mL). The organic phase was separated, dried over anhydrous sodium sulfate, filtered and concentrated to dryness. The residue was purified by silica gel chromatography [petroleum ether: ethyl acetate = 3:11 to afford compound B-l (3.1 g, 66% yield) as a pale yellow solid. ?H-NMR (DM50-cl6, 400 MHz): 7.84-7.82 (d, J=8.8 Hz, 1H), 7.65-7.64 (d, J=1.2 Hz, 1H), 7.33-7.3 1 (dd, J=1.2 Hz, J=8.8 Hz, 1H), 6.52 (s, 2H).

Reference： [1]Patent: WO2017/27600,2017,A1 .Location in patent: Paragraph 00256; 00257
[2]Tetrahedron Letters,1996,vol. 37,p. 2885 - 2886

5
[ 546-88-3 ]
[ 394-47-8 ]
[ 36216-80-5 ]

Yield	Reaction Conditions	Operation in experiment
53.7%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃;	2- fluorobenzonitrile (6.1g, 50.0mmol), acetohydroxamic acid (5.6g, 75.0mmol) and potassium carbonate (10.4g, 75mmol) was dissolved in DMF (40mL), the mixture was stirred overnight and heated to 80 .With ethyl acetate (100mL × 2) and extracted.The combined organic phases were washed with water (100 mL × 2), saturated brine (100 mL), dried over anhydrous sodium sulfate.Filtered, and the solvent was evaporated under reduced pressure and the crude product purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 4/1), as a white solid (3.6g, 53.7%).

Reference： [1]Tetrahedron Letters,1996,vol. 37,p. 2885 - 2886
[2]Patent: CN104530046,2016,B .Location in patent: Paragraph 0202; 0203; 0204; 0205

6
[ 546-88-3 ]
[ 38469-83-9 ]
[ 157368-82-6 ]

Reference： [1]Tetrahedron Letters,1996,vol. 37,p. 2885 - 2886

7
[ 546-88-3 ]
[ 94088-46-7 ]
[ 177995-40-3 ]

Reference： [1]Tetrahedron Letters,1996,vol. 37,p. 2885 - 2886

8
[ 546-88-3 ]
[ 105942-08-3 ]
[ 177995-39-0 ]

Yield	Reaction Conditions	Operation in experiment
63%		Step A: 6-Bromobenzo[d]isoxazol-3-amine: N-hydroxyacetamide (1.13 g, 15.0 mmol) was dissolved in DMF (20 mL). To this was added KOt-Bu (1.68 g, 15.0 mmol) and the reaction was stirred for 30 minutes before addition of 4-bromo-2-fluorobenzonitrile (2.0 g, 10.0 mmol). The reaction mixture was left at ambient temperature for 2 hours, then diluted with ethyl acetate (50 mL) and water (50 mL). The aqueous layer was extracted with ethyl acetate The combined organics were washed with water, dried, filtered and concentrated. The crude product was purified by flash column chromatography, eluting with ethyl acetate/hexanes (1:4), ethyl acetate/hexanes (1:3) to give the desired product (1.35 g, 63%). MS (APCI) m/z 215.2, 217.1 (M+1).

Reference： [1]Tetrahedron Letters,1996,vol. 37,p. 2885 - 2886
[2]Patent: US2007/49603,2007,A1 .Location in patent: Page/Page column 61-62
[3]Patent: WO2010/51042,2010,A1 .Location in patent: Page/Page column 135
[4]Patent: WO2014/151147,2014,A1 .Location in patent: Paragraph 00502
[5]Patent: US2014/357651,2014,A1 .Location in patent: Paragraph 0485
[6]Patent: US9174994,2015,B2 .Location in patent: Page/Page column 118

9
[ 546-88-3 ]
2-fluoro-4-(methoxymethyl)benzonitrile [ No CAS ]
6-(methoxymethyl)benzo[d]isoxazol-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide
62%	Stage #1: acetylhydroxamic acid With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: 2-fluoro-4-(methoxymethyl)benzonitrile In N,N-dimethyl-formamide at 20 - 40℃;	xxvi.b b) 6-(Methoxymethyl)benzo[d]isoxazol-3-amine I62 b) 6-(Methoxymethyl)benzo[d]isoxazol-3-amine I62 To a solution of acetohydroxamic acid (1.5 g, 9.1 mmol) in DMF (50 mL) was added t-BuOK (3.06 g, 27.2 mmol) and the mixture was stirred at RT for 1 h. 2-Fluoro-4- (methoxymethyl)benzonitrile I61 (1.5 g, 9.1 mmol) was then added and the mixture was heated at 40 °C overnight. [93] The mixture was diluted with water and extracted with EtOAc. The organic extract was concentrated under reduced pressure and the residue was purified by silica gel chromatography (Pet. ether/EtOAc = 100/1 to 10/1) to give the title compound (1 g, 62%) as a yellow solid. LCMS-D: Rt 0.95 min, m/z 179.0 [M+H]+.

Reference： [1]Palermo [Tetrahedron Letters, 1996, vol. 37, # 17, p. 2885 - 2886]
[2]Current Patent Assignee: CANCER THERAPEUTICS CRC PTY LTD - WO2019/243491, 2019, A1 Location in patent: Page/Page column 92-93

10
[ 546-88-3 ]
[ 108-91-8 ]
[ 1124-53-4 ]

Yield	Reaction Conditions	Operation in experiment
33%	With sodium periodate In methanol; water Ambient temperature;

Reference： [1]Atkinson, Robert N.; Storey, Bernadette M.; King, S. Bruce [Tetrahedron Letters, 1996, vol. 37, # 52, p. 9287 - 9290]

11
[ 16927-00-7 ]
[ 546-88-3 ]
[ 100-69-6 ]
2-(2-pyridyl)ethyl acetohydroxamate [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin Transactions 2 (2001),2001,p. 778 - 781

12
C₂₆H₂₆FN₅O₄ [ No CAS ]
[ 546-88-3 ]
C₂₆H₂₈N₆O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With potassium carbonate In DMF (N,N-dimethyl-formamide); water at 20℃;	37.J Part J: Acetohydroxamic acid (0.096 g, 1.28 mmol), potassium carbonate (0.35 g, 2.57 mmol), 3 mL of DMF and 1 mL of water were stirred together for 10 minutes at rt then the product from above (0.21 g, 0.43 mmol) in 2 mL of DMF was added and the reaction stirred overnight. Next EtOAc was added and the mixture transferred to a separatory funnel where it was washed 5×with water then brine and dried over sodium sulfate to give the amino benzisoxazole compound (0.16 g, 76% yield) LRMS (ES+) 505.5 (M+H)+.

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US2003/232804, 2003, A1 Location in patent: Page 102

13
[ 546-88-3 ]
[ 454-91-1 ]
[ 210840-49-6 ]

Yield	Reaction Conditions	Operation in experiment
59.5%	With thionyl chloride; potassium carbonate; In ethyl acetate; N,N-dimethyl-formamide; toluene;	Example 3-1 Synthesis of O-{1-(3-trifluoromethylphenyl)ethyl}-acetohydroxamate A 20 mg portion of DMF was added to 5 ml of toluene solution containing 3 g (15.8 mmol) of 1-(3-trifluoromethylphenyl)ethylalcohol. Then, 2.25 g (18.9 mmol) of thionyl chloride was added under ice-cooling. After 2 hours of stirring at 10C or less, this was concentrated under a reduced pressure on a water bath at temperature of 50 to 60C. After cooling to room temperature, 8 ml of DMF, 3.3 g (23.9 mmol) of anhydrous potassium carbonate and 2.15 g (20.5 mmol) of acetohydroxamic acid were added, and the mixture was stirred for 6 hours while heating at 120 to 130C. After cooling, ethyl acetate was added to the reaction mixture, and the mixture was washed with water and saturated brine in that order and then dried over anhydrous sodium sulfate. This was concentrated under a reduced pressure, and the resulting residue was purified by a silica gel column chromatography (n-Hex:AcOEt = 1:1 ? 1:2) to give 2.32 g of the title compound (yield = 59.5%). Melting point; 75.3 - 76.5C 1H-NMR delta (CDCl3); 1.57 (3H, d), 1.8 - 2.2 (3H, br), 4.8 - 5.15 (1H, br), 7.45 - 7.55 (4H, m), 7.8 - 8.0 (1H, br)

Reference： [1]Patent: EP949243,1999,A1

14
[ 546-88-3 ]
[ 1086626-59-6 ]
[ 1086625-63-9 ]

Yield	Reaction Conditions	Operation in experiment
74%	Stage #1: acetylhydroxamic acid With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 2-fluoro-5-(6-(2-isobutoxyphenyl)-2-oxo-1,2-dihydropyrimidin-4-yl)benzonitrile In N,N-dimethyl-formamide at 20℃; for 16h; Stage #3: In N,N-dimethyl-formamide Acidic conditions;	23 EXAMPLE 23 4-(3-amino-l,2-benzisoxazol-5-yl)-6-{2-[(2-methylpropyl)oxy]phenyl}pyrimidin-2(lH)-one [00203] To a solution of acetohydroxamic acid (53 mg, 0.7 mmol) in DMF (5 mL) was added potassium ter/-butoxide (80 mg, 1.76 mmol). The mixture was stirred at room temperature for 20 min, followed by the addition of solution of 2-fluoro-5-(6-(2-isobutoxyphenyl)-2-oxo-l,2- dihydropyrimidin-4-yl)benzonitrile (100 mg, 0.27 mmol) (Example l^Step 4) in DMF (4 mL). The reaction was stirred at room temperature for 16h. The mixture was quenched by acid and the product was purified by Prep-HPLC to give 75 mg (74%) of 4-(3 -amino- 1 ,2-benzisoxazol- 5-yl)-6-{2-[(2-methylpropyl)oxy]phenyl} pyrimidin-2(lH)-one. 1H NMR (400 MHz, d6- DMSO): δ 1 1.80 (s, br, 2H), 8.78 (s, IH), 8.37 (d, IH), 7.66-7.45 (m, 3H), 7.24-7.00 (m, 3H), 6.60 (s, 2H), 3.83 (d, 2H), 2.05-1.97 (m, IH), 0.98 (d, 6H). MS (EI) for C21H20N4O3: 377 (MH+).

Reference： [1]Current Patent Assignee: EXELIXIS INC - WO2008/143759, 2008, A1 Location in patent: Page/Page column 55-56

15
[ 909185-86-0 ]
[ 546-88-3 ]
[ 909185-92-8 ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: acetylhydroxamic acid With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃; for 0.5h; Inertt atmosphere; Stage #2: 2-fluoro-3-iodo-4-methylbenzonitrile In N,N-dimethyl-formamide at 20℃;	11 INTERMEDIATE 11 7-lodo-6-methyl-1,2-benzisoxazol-3-amine [Show Image] Potassium tert-butoxide (3.58 g, 31.87 mmol) was added to a stirred suspension of N-hydroxyacetamide (2.39 g, 31.87 mmol) in N,N'-dimethylformamide (44 mL) at room temperature under argon. After 30 minutes, 2-fluoro-3-iodo-4-methylbenzonitrile (Intermediate 10b, 3.33 g, 12.75 mmol) was added to the stirred reaction mixture at room temperature. After stirring overnight, the solvent was evaporated under reduced pressure, and the residue was partitioned between satured aqueous ammonium chloride solution and ethyl acetate. The organic layer was washed with brine, dried (MgS04) and evaporated. Purification of the residue by flash chromatography (4:1 hexanes/ethyl acetate to 1:1 hexanes/ethyl acetate) gave the title compound (2.21 g, 63%) as a pale yellow solid. LRMS (m/z): 275 (M+1)+.1H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.59 (s, 3 H) 4.39 (br. s., 2 H) 7.15 (d, J=7.97 Hz, 1 H) 7.37 (d, J=7.97 Hz, 1 H)
63%	Stage #1: acetylhydroxamic acid With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃; for 0.5h; Inert atmosphere; Stage #2: 2-fluoro-3-iodo-4-methylbenzonitrile In N,N-dimethyl-formamide at 20℃;	11 INTERMEDIATE 11; 7-lodo-6-methyl-1,2-benzisoxazol-3-amine; Potassium tert-butoxide (3.58 g, 31.87 mmol) was added to a stirred suspension of N- hydroxyacetamide (2.39 g, 31.87 mmol) in Λ/,Λ/'-dimethylformamide (44 mL) at room temperature under argon. After 30 minutes, 2-fluoro-3-iodo-4-methylbenzonitrile (Intermediate 10b, 3.33 g, 12.75 mmol) was added to the stirred reaction mixture at room temperature. After stirring overnight, the solvent was evaporated under reduced pressure, and the residue was partitioned between satured aqueous ammonium chloride solution and ethyl acetate. The organic layer was washed with brine, dried (MgS04) and evaporated. Purification of the residue by flash chromatography (4:1 hexanes/ethyl acetate to 1 :1 hexanes/ethyl acetate) gave the title compound (2.21 g, 63%) as a pale yellow solid.LRMS (m/z): 275 (M+1)+.1 H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.59 (s, 3 H) 4.39 (br. s., 2 H) 7.15 (d, J=7.97 Hz, 1 H) 7.37 (d, J=7.97 Hz, 1 H)

Reference： [1]Current Patent Assignee: ALMIRALL SA - EP2322176, 2011, A1 Location in patent: Page/Page column 25
[2]Current Patent Assignee: ALMIRALL SA - WO2011/57757, 2011, A1 Location in patent: Page/Page column 42-43

16
[ 546-88-3 ]
[ 1185040-54-3 ]
[ 1173701-23-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium periodate In methanol at 20℃;
	With sodium periodate In methanol; water at 20℃; for 16.0833h;	11 Example 11: (24)To a stirred solution of 22 (5 g, 27.1 mmol) in 2,2-dimethoxypropane (80 ml_) was added p-toluenesulfonic acid (catalytic amount) at room temperature. After complete consumption of starting material (TLC analysis), the solution was cooled 0 °C before the addition of H2O (10 ml_). On a preparative scale the intermediate acetonide was not isolated (analytical samples were purified via flash column chromatography with a solvent system of 3:1 (hexanes-ethyl acetate)). Data for the intermediate 23: Rf 0.56 (1 :1 hexanes/ethyl acetate); [α]D23 +74.6 (c 4.02, CHCI3); IR (film): v 3018, 2987, 2936, 1712, 1651 , 1425, 1380, 1259, 1155, 1031 , 917, 856, 697, 667, 512 cm"1; 1H NMR (300 MHz, CDCI3) δ 7.06 (dd, J = 5.3, J = 3.1 Hz, 1 H), 4.84 (d, J = 5.7 Hz, 1 H), 4.28-4.41 (m, 1 H), 4.07-4.26 (m, 2H), 2.21-2.45 (m, 1 H), 1.99-2.16 (m, 1 H), 1.86-1.99 (m, 1 H), 1.58-1.72 (m, 1 H), 1.33 (d, J = 10.2 Hz, 6H), 1.24 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (75 MHz, CDCI3) δ 166.2, 142.3, 130.0, 108.5, 72.6, 70.4, 60.5, 27.8, 26.2, 25.1 , 20.9, 14.2 ppm; MS (El) m/z (%): 226 (M+-CH3), 211 (77), 181(15), 169(17), 123(100), 105(17), 95(13), 83(11), 79(76), 67(14), 59(10), 55(11), 43(82), 41 (14); HRMS (M+-CH3) calcd for Ci2H16O4 211.0970, found 211.0969; Anal, calcd: C 64.27; H 7.19. Found C 64.52; H 7.08.NaIO4 (5.80 g, 27.1 mmol) was added to the reaction vessel prior to the addition of a solution of acetohydroxamic acid (2.03 g, 27.1 mmol) in MeOH (25 mL) dropwise over 5 minutes. The resulting solution was stirred at room temperature for 16 h, quenched by the slow addition of sat. NaHSO3 (10 mL) and extracted into Et2O (3 x 100 mL). The combined organic layers were washed with brine (2 x 30 mL) and dried over Na2SO4. The crude material was purified via flash column chromatography with a solvent system of 2:8 (hexanes-ethyl acetate) to yield 24 (5.65 g, 70% over 2 steps) as a white solid: Rf 0.33 (3:7 hexanes- ethyl acetate); mp 89-90 °C (hexanes-ethyl acetate); [α]D23 -18.0 (c 0.54, CHCI3); IR (film) v 3466, 2938, 2987, 1747, 1684, 1620, 1372, 1275, 1086 cnT1; 1H NMR (600 MHz, CDCI3) δ 6.57-6.65 (m, 2H), 5.47-5.52 (m, 1 H), 4.71 (d, J = 6.8 Hz, 1 H), 4.56 (dd, J = 4.7, 6.6 Hz, 1 H), 4.38 (q, J = 7.2 Hz, 2H), 2.01 (s, 3H), 1.38 (t, J = 7.2 Hz, 3H), 1.32 (s, 3H), 1.30 (s, 3H) ppm; 13C NMR (150 MHz, CDCI3) δ 173.9, 166.6, 132.4, 128.4, 111.7, 79.2, 76.1 , 72.8, 62.7, 50.0, 25.6, 25.4, 21.7, 14.1 ppm; MS (El) m/z (%): 297 (M), 43(100), 96(30), 100(32), 105(35), 124(52); HRMS calcd for C14H19NO6 297.1212, found 297.1215.
5.65 g	With sodium periodate In methanol at 20℃; for 16.2h; Inert atmosphere; regioselective reaction;

5.65 g	With sodium periodate In methanol at 20℃; for 16h; Inert atmosphere;
	With sodium periodate In methanol at 20℃; for 16h;	2 NalO4 (5.80 g, 27.1 mmol) was added to the reaction mixture above prior to the dropwise addition of a solution of acetohydroxamic acid (2.03 g, 27.1 mmol) in MeOH (25 mL) over 5 minutes. The resulting solution was stirred at room temperature for 16 h then diluted with ethyl acetate (300 mL). Inorganic precipitate was filtered off and resulting solution was washed with saturated solution of NaHCO3(2 x 20 mL). Organic layer was dried over Mg2SO4 and evaporated. The crude material was purified via flash column chromatography [hexane-ethyl acetate (1 :4)] to yield oxazine 5 (5.65 g, 70% over 2 steps) as a white solid; mp 89-90 °C (hexanes-ethyl acetate): Rf 0.33 (3:7 hexane- ethyl acetate); [a]23D = -18.0 (c 0.54, CHCI3); IR (film, cm"1) v 3466, 2938, 2987, 1747, 1684, 1620, 1372, 1275, 1086; 1H NMR (600 MHz, CDCI3) δ 6.57-6.65 (m, 2H), 5.47-5.52 (m, 1 H), 4.71 (d, J = 6.8 Hz, 1 H), 4.56 (dd, J = 4.7, 6.6 Hz, 1 H), 4.38 (q, J = 7.2 Hz, 2H), 2.01 (s, 3H), 1.38 (t, J = 7.2 Hz, 3H), 1.32 (s, 3H), 1.30 (s, 3H); 13C NMR (150 MHz, CDCI3) δ 173.9, 166.6, 132.4, 128.4, 1 1 1.7, 79.2, 76.1 , 72.8, 62.7, 50.0, 25.6, 25.4, 21.7, 14.1 ; MS (El) m/z (%): 297 (M+), 124(52), 105(35), 100(32), 96(30), 43(100); HRMS. Calcd for Ci4H19NO6: 297.1212. Found: 297.1215.
5.65 g	With sodium periodate In methanol at 20℃; for 16h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Werner, Lukas; Hudlicky, Jason Reed; Wernerova, Martina; Hudlicky, Tomas [Tetrahedron, 2010, vol. 66, # 21, p. 3761 - 3769]
[2]Current Patent Assignee: BROCK UNIVERSITY - WO2009/137916, 2009, A1 Location in patent: Page/Page column 61-62
[3]Location in patent: experimental part Fabris, Fabrizio; Collins, Jonathan; Sullivan, Bradford; Leisch, Hannes; Hudlicky, Tomas [Organic and Biomolecular Chemistry, 2009, vol. 7, # 12, p. 2619 - 2627]
[4]Werner, Lukas; Machara, Ales; Hudlicky, Tomas [Advanced Synthesis and Catalysis, 2010, vol. 352, # 1, p. 195 - 200]
[5]Current Patent Assignee: BROCK UNIVERSITY - WO2011/47466, 2011, A1 Location in patent: Page/Page column 47
[6]Location in patent: experimental part Werner, Lukas; Machara, Ales; Sullivan, Bradford; Carrera, Ignacio; Moser, Michael; Adams, David R.; Hudlicky, Tomas; Andraos, John [Journal of Organic Chemistry, 2011, vol. 76, # 24, p. 10050 - 10067]

17
[ 546-88-3 ]
[ 100-46-9 ]
[ 6957-05-7 ]

Yield	Reaction Conditions	Operation in experiment
83%	Stage #1: acetylhydroxamic acid With 4-methyl-morpholine; dimethylbromosulphonium bromide In 1,2-dichloro-ethane at 0℃; for 2h; Inert atmosphere; Stage #2: benzylamine In 1,2-dichloro-ethane at 0 - 80℃;	General procedure for the synthesis of unsymmetrical urea derivatives 6: To a solution of hydroxamic acid 1 (1 mmol) in DCE (2 mL) at 0 °C under nitrogen atmosphere, N-methylmorpholine (NMM) (2.6 mmol) then bromodimethylsulfonium bromide 2 (BDMS) (1.3 mmol) were added and the mixture was stirred at 0 °C for 2 h. The amine 5 (1.2 mmol) was then added and the temperature of reaction mixture was raised to 80 °C and stirred at the same temperature for 7-18 h (Table 2). Upon completion of the reaction as indicated by TLC, the reaction mixture was cooled to rt and acidified with 2 mL HCl (0.1 N) and the solution was extracted with DCM (2 × 10 mL) and EtOAc (1 × 10 mL). The combined organic phase was dried over MgSO4, filtered, and evaporated under reduced pressure. The resulting crude product was purified by silica gel column chromatography using a gradient mixture of hexane/ethyl acetate as eluent to give the corresponding pure urea derivatives 6. All the products are known compounds and were characterized by the comparison of their mp and spectral data with those of reported in the literature. [10] and [12]
76%	Stage #1: acetylhydroxamic acid With 4-methyl-morpholine; 1,3,5-trichloro-2,4,6-triazine In dichloroethane at 0℃; for 1.5h; Inert atmosphere; Stage #2: benzylamine In dichloroethane at 0 - 84℃; for 15h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Yadav, Deepak K.; Yadav, Arvind K.; Srivastava, Vishnu P.; Watal, Geeta; Yadav, Lal Dhar S. [Tetrahedron Letters, 2012, vol. 53, # 23, p. 2890 - 2893]
[2]Location in patent: experimental part Hamon, Florian; Prié, Gildas; Lecornué, Frédéric; Papot, Sébastien [Tetrahedron Letters, 2009, vol. 50, # 49, p. 6800 - 6802]

18
[ 546-88-3 ]
[ 68325-15-5 ]
[ 114080-94-3 ]

Yield	Reaction Conditions	Operation in experiment
41%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	Intermediate 1 : lsoxazolo[5,4-cipyridin-3-ylamine.; To a solution of 3-chloro-isonicotinitrile (1.13 g, 8.36 mmol) in DMF (6.0 mL) were added potassium carbonate (1.69 g, 12.2 mmol) and acetohydroxamic acid (0.91 g, 12.2 mmol). The reaction mixture was stirred at rt overnight, diluted with EtOAc (200 mL) and extracted with saturated aqueous NaHCO3 (200 mL) then saturated aqueous NaCI (100 mL). The aqueous layers were back extracted with EtOAc (200 mL) and the combined organic layers were dried (MgSO4) and concentrated. The crude residue was purified (FCC, 2 N NH3 in MeOH/DCM) to give isoxazolo[5,4-c]pyhdin-3-ylamine (0.447 g, 41 %). MS (ESI+): calcd for C6H5N3O m/z 135.04, found 136.2 (M+H)+. 1H NMR (d6-DMSO): 8.93 (d, J = 0.8, 1 H), 8.45 (d, J = 5.2, 1 H), 7.88-7.86 (dd, J = 5.2, 1.2, 1 H), 6.72 (br s, 2H).

Reference： [1]Patent: WO2010/68452,2010,A1 .Location in patent: Page/Page column 26
[2]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 7357 - 7362

19
[ 546-88-3 ]
[ 179897-89-3 ]
[ 455280-00-9 ]

Yield	Reaction Conditions	Operation in experiment
86%		xv) 5-Bromobenzo[d]isoxazol-3-amine I40 To a solution of acetohydroxamic acid (23.7 g, 0.315 mol) in DMF (800 ml.) at 0 C under N2 was added t-BuOK (35.4 g, 0.315 mol) and the mixture was stirred at 15 C for 2 h. 5-Bromo-2-fluorobenzonitrile (21.0 g, 0.105 mol) was then added and the mixture was stirred at RT overnight. The mixture was diluted with EtOAc (1.5 L) and washed with water (400 ml. x 4). The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure. The residue was purified by column chromatography (Pet. ether/EtOAc = 50/1 to 3/1) to give the title compound (19 g, 86%) as a white solid. LCMS-D: Rt2.13 min; m/z 212.9/214.9 [M+H]+.
62%		The title compound was prepared by a modification of the literature procedure as described in Palermo, M. G., Tetrahedron Lett, 37:2885 (1996). A single neck 50 mL flask equipped with a magnetic stirred was charged with N-hydroxyacetamide (2.63 g, 35.0 mmol) and DMF (100 mL). Then, KOtBu (3.93 g, 35.0 mmol) was added in one portion. The temperature rose to 300C. The mixture was stirred for Ih and, 5-bromo~2-fluorobenzonitrile (7 g, 35.0 mmol) was added. The reaction mixture was stirred for overnight. A further portion of KOtBu (1.96 g, 17.5mmo) was added and the solution was again stirred overnight. The mixture was poured into brine and CH2CI2 and the layers were separated. The organic phase was dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash column chromatography (BIOTAGE, eluting with a gradient of 0 to 40% EtOAc in hexanes) to afford the title compound (4.59 g, 62%) as a colorless solid. 1H NMR (500 MHz, DMSOd6) delta 8.09 (d, J = 1.8 HZ, IH), 7.65 (dd, J = 2.1, 8.9 Hz, IH), 7.45 (d, J = 8.9 Hz5 IH), 6.49 (s, 2H). LCMS: Anal. Calcd. for C7H5BrN2O: 2115 213; found: 212, 214 (M+H)+.

Reference： [1]Patent: WO2019/243491,2019,A1 .Location in patent: Page/Page column 83
[2]Patent: WO2010/138488,2010,A1 .Location in patent: Page/Page column 57-58
[3]Patent: WO2010/51042,2010,A1 .Location in patent: Page/Page column 134
[4]Patent: WO2014/151147,2014,A1 .Location in patent: Paragraph 00502
[5]Patent: US2014/357651,2014,A1 .Location in patent: Paragraph 0485

20
[ 546-88-3 ]
[ 3939-13-7 ]
[ 92914-74-4 ]

Yield	Reaction Conditions	Operation in experiment
28%		Synthesis of intermediate VX001: Isoxazolo[5,4-b]pyridin-3-amine 909 mg (8.1 mmol) of KO-t-Bu were added, with vigorous stirring, to a suspension of 668 mg (8.9 mmol) of acethydroxamic acid in DMF (20 ml), and the mixture was stirred for 30 min at RT. 990 mg (8.1 mmol) of 2-fluoro-nicotinonitrile were then added, and stirring was carried out for a further 5 h at 50 C. The mixture was then extracted with EA and the organic phase was dried over Na2SO4, filtered and concentrated in vacuo. CC (hexane/EA 7:3) of the residue yielded 305 mg (2.3 mmol, 28%) of isoxazolo[5,4-b]pyridin-3-amine.

Reference： [1]Patent: US2010/234419,2010,A1 .Location in patent: Page/Page column 15

21
[ 95104-21-5 ]
[ 546-88-3 ]
[ 111043-13-1 ]

Yield	Reaction Conditions	Operation in experiment
25%		Synthesis of intermediate VX007: Isoxazolo[5,4-b]quinolin-3-amine 2.52 g (22.5 mmol) of KO-t-Bu were added to a solution of 1.69 g (22.5 mmol) of acethydroxamic acid in THF (45 ml), and stirring was carried out for 30 min at RT. The mixture was then cooled to 0 C., and 2.85 g (15.0 mmol) of <strong>[95104-21-5]2-chloroquinoline-3-carbonitrile</strong> and 1.22 g (3.8 mmol) of Cs2CO3 were added in succession. The reaction solution was stirred for 3 h at RT and then diluted with EA, and washing with water and brine was carried out. The organic phase was dried over Na2SO4, filtered and concentrated in vacuo. CC (DCM/MeOH 97:3) of the residue yielded 700 mg (3.8 mmol, 25%) of isoxazolo[5,4-b]quinolin-3-amine.

Reference： [1]Patent: US2010/234419,2010,A1 .Location in patent: Page/Page column 15

22
[ 546-88-3 ]
[ 1897-52-5 ]
[ 904815-05-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: acetylhydroxamic acid With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃; for 0.75h; Stage #2: 2,6 difluorobenzonitrile In N,N-dimethyl-formamide at 50℃; for 16h;	4 4.00 g (35.65 mmol) of potassium tert-butoxide and 2.60 g (34.64 mmol) of acetohydroxamic acid are dissolved in 50 ml of dry dimethylformamide and stirred at room temperature for 45 minutes. After the addition of 3.30 g (23.72 mmol) of 2,6-difluorobenzonitrile, the mixture is stirred at 50° C. for 16 hours. The mixture is concentrated under reduced pressure, and the residue is dissolved in dichloromethane and washed with water. After drying and concentration of the organic phase, 3.2 g of a yellow resin are obtained, which, according to 1H NMR, is about 85% pure

Reference： [1]Current Patent Assignee: BAYER AG - US2010/267703, 2010, A1 Location in patent: Page/Page column 19

23
[ 221202-14-8 ]
[ 546-88-3 ]
[ 1228574-42-2 ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: acetylhydroxamic acid With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: 2-(difluoromethoxy)-6-fluorobenzonitrile In N,N-dimethyl-formamide at 20 - 60℃; for 19h;	5 8.00 g (71.29 mmol) of potassium tert-butoxide and 5.20 g (69.27 mmol) of acetohydroxamic acid are dissolved in 50 ml of dry dimethylformamide and stirred at room temperature for 1 hour. After the addition of 4.40 g (23.51 mmol) of 2-(difluoromethoxy)-6-fluorobenzonitrile, the mixture is stirred first at room temperature for 3 hours and then at 60° C. for 16 hours. The mixture is concentrated under reduced pressure, the residue is stirred with water and the pale olive-coloured precipitate is filtered off with suction. This gives 4.4 g of product, which, according to LC-MS, is about 89% pure

Reference： [1]Current Patent Assignee: BAYER AG - US2010/267703, 2010, A1 Location in patent: Page/Page column 19

24
[ 546-88-3 ]
[ 179232-29-2 ]
[ 65685-51-0 ]

Yield	Reaction Conditions	Operation in experiment
31%		Step A: 6-bromobenzo[d]isoxazol-3-ol: N-hydroxyacetamide (0.99 g, 12.9 mmol) was dissolved in DMF (20 mL). To this was added KOt-Bu (1.44 g, 12.9 mmol) and the reaction was stirred for 30 minutes before addition of methyl 4-bromo-2-fluorobenzoate (2.0 g, 8.58 mmol). The reaction mixture was stirred at ambient temperature for 10 days, then diluted with ethyl acetate (50 mL) and 1N NaOH (50 mL). The aqueous layer was washed with ethyl acetate, then acidified with 2N HCl (30 mL). The desired product was collected by filtration (570 mg, 31%).

Reference： [1]Patent: US2007/49603,2007,A1 .Location in patent: Page/Page column 62

25
[ 546-88-3 ]
[ 4088-84-0 ]
[ 868271-14-1 ]

Yield	Reaction Conditions	Operation in experiment
76.7%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃;	2-Fluoro-5-trifluoro-benzonitrile (Matrix, 5 g, 26.4 mmol), N-hydroxy-acetamide (Aldrich, 2.9 g, 39.7 mmol) and K2CO3 (5.48 g, 39.7 mmol) in DMF (20 mL) were heated at 80 C overnight. The reaction was partitioned between ethyl acetate and water. The aqueous layer was extracted two times with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give the crude material, which was purified by silica gel column (hexanes: ethyl acetate 2:1 ) to afford the title compound as white solid (4.1 g, 76.7%). MS: 203 (MH+).
76.6%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃;	Step A 5-Trifluoromethyl-benzo[d]isoxazol-3-ylamine 2-Fluoro-5-trifluoro-benzonitrile (Matrix, 5 g, 26.4 mmol), N-hydroxy-acetamide (Aldrich, 2.9 g, 39.7 mmol) and K2CO3 (5.48 g, 39.7 mmol) in DMF (20 mL) were heated at 80 C. overnight. The reaction was partitioned between ethyl acetate and water. The aqueous layer was extracted two times with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give the crude material, which was purified by silica gel column (hexanes:ethyl acetate 2:1) to afford the title compound as white solid (4.1 g, 76.7%). MS: 203 (MH+).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 6042 - 6048
[2]Patent: US2011/306592,2011,A1 .Location in patent: Page/Page column 51

26
[ 546-88-3 ]
[ 16858-01-8 ]
[ 7646-79-9 ]
Co(III)(tris(2-pyridylmethyl)amine)(acetohydroximate)(Cl) [ No CAS ]

Reference： [1]Inorganic Chemistry,2012,vol. 51,p. 9350 - 9356,7

27
[ 546-88-3 ]
[ 89284-61-7 ]
[ 1229383-25-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 7357 - 7362

28
[ 546-88-3 ]
[ 38180-46-0 ]
[ 114080-93-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 7357 - 7362

29
[ 546-88-3 ]
[ 1448675-03-3 ]
[ 1448675-04-4 ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: acetylhydroxamic acid With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 0 - 20℃; for 1h; Inert atmosphere; Stage #2: 2-fluoro-4-((tetrahydro-2 H-pyran-2-yl)oxy)benzonitrile In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	xi.b 6-((Tetrahydro-2H-pyran-2-yl)oxy)benzo[d]isoxazol-3-amine I30 [78] To a solution of acetohydroxamic acid (13.7 g, 182.3 mmol) in DMF (60 ml.) at 0 °C under N2was added potassium tert- butoxide (20.4 g, 182.3 mmol) and the mixture was stirred at RT for 1 h. 2-Fluoro-4-((tetrahydro-2H-pyran-2-yl)oxy)benzonitrile I29 (13.4 g, 60.8 mmol) was then added and the mixture was stirred at RT overnight. EtOAc (500 ml.) was added and the mixture was washed with water (100 ml. x 5). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Pet. ether/EtOAc = 100/1 to 5/1) to give the title compound (12.1 g, 85%) as a white solid. LCMS-D: Rt2.31 min; m/z 235.1 [M+H]+.
69%	Stage #1: acetylhydroxamic acid With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: 2-fluoro-4-((tetrahydro-2 H-pyran-2-yl)oxy)benzonitrile In N,N-dimethyl-formamide at 20℃; for 24h;	3.85.2 Step 2: 6-(Tetrahydro-pyran-2-yloxy)-benzo[d]isoxazol-3-ylamine (3_85_3) Step 2: 6-(Tetrahydro-pyran-2-yloxy)-benzo[d]isoxazol-3-ylamine (3_85_3) [00540] Potassium tert-butoxide (8.96 g, 80 mmol) was added in portions to a solution of N-hydroxy acetamide (6.00 g, 80 mmol) in N,N-dimethylformamide (40 mL). After the addition was complete, the resulting mixture was stirred at room temperature for 1 hour. A solution of 2-fluoro-4-(tetrahydro-2H-pyran-2-yloxy)benzo- nitrile 3_85_2 (8.90 g, 40 mmol) in ,Ν-dimethylformamide (20 mL) was added and the resulting mixture was stirred at room temperature for 24 hours and concentrated. The residue was diluted with ethyl acetate (200 mL), washed with water (20 mL) and brine (20 mL), dried and concentrated. The residue was purified by column chromatography to give compound 3_85_3 (6.5 g, 69 % yield).

Reference： [1]Current Patent Assignee: CANCER THERAPEUTICS CRC PTY LTD - WO2019/243491, 2019, A1 Location in patent: Page/Page column 78
[2]Current Patent Assignee: AICURIS GMBH & CO. KG - WO2013/110643, 2013, A1 Location in patent: Paragraph 00540

30
[ 546-88-3 ]
methyl (2R)-2-bromo-3-(2-naphthyl)propanoate [ No CAS ]
C₁₆H₁₇NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: acetylhydroxamic acid With sodium hydride In N,N-dimethyl-formamide; mineral oil for 0.333333h; Cooling with ice; Stage #2: methyl (2R)-2-bromo-3-(2-naphthyl)propanoate In N,N-dimethyl-formamide; mineral oil at 20℃; for 16h;	6 Synthesis of KOK2015 (Step 6) Acetohydroxamic acid (31 mg, 0.41 mmol) was dissolved in N,N-dimethylformamide (3 ml). To this, sodium hydride (60%) (16 mg, 0.41 mmol) was added under ice cooling and stirred for 20 minutes. To the mixture, an N,N-dimethylformamide (3 ml) solution containing KOK1164 (100 mg, 0.34 mmol) obtained in Step 2 was added dropwise and stirred at room temperature for 16 hours. To the mixture, water was added and the mixture was extracted three times with ethyl acetate, washed three times with water and then washed with a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate. This was filtered and concentrated under reduced pressure. Thereafter, the residue was purified by silica gel column chromatography (hexane : ethyl acetate = 1 : 1) to obtain the titled compound (colorless oily substance: 79 mg, 81 %). 1H-NMR (DMSO-d6, 270 MHz) δ ppm: 1.72 (3H, s), 3.21 (2H, d, J = 6.3 Hz), 3.61 (3H, s), 4.71 (1H, t, J = 6.3 Hz), 7.34-7.54 (3H, m), 7.73-7.92 (4H, m), 11.12 (1H, s).

Reference： [1]Current Patent Assignee: YOKOHAMA CITY UNIVERSITY; NATIONAL AGRICULTURE AND FOOD RESEARCH ORGANIZATION; INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH (RIKEN) - EP2682383, 2014, A1 Location in patent: Paragraph 0097; 0098; 0099

31
[ 23364-44-5 ]
[ 708-76-9 ]
[ 546-88-3 ]
[ 1686-22-2 ]
(acetohydroxamato-κ²O,O'){1S,2R(+)-2-[(1-oxido-1,2-diphenylethyl)iminomethyl]-3,5-dimethoxyphenolato-κ³N,O,O'}oxidovanadium(V) [ No CAS ]
(acetohydroxamato-κ²O,O'){(+)-2-[(1-oxido-1,2-diphenylethyl)iminomethyl]-3,5-dimethoxyphenolato-κ³N,O,O'}oxidovanadium(V) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (1S,2R)-2-Amino-1,2-diphenylethanol; 2-hydroxy-4,6-dimethoxybenzaldehyde; acetylhydroxamic acid In ethanol for 1h; Reflux; Stage #2: vanadium(V) oxytriethoxide In ethanol at 20℃; for 2h; Overall yield = 80 %;	14 Synthesis of vanadium(V) complexes General procedure: 2.4. Synthesis of vanadium(V) complexesThe complexes were obtained in the following exampleprocedure. A solution of 5 mmol of 1S,2R(+)-2-amino-1,2-diphenylethanol in absolute ethanol (10 ml) was added withstirring to 5 mmol of an aromatic o-hydroxyaldehyde (salicy-laldehyde, 3-methoxysalicylaldehyde, 5-methoxysalicylaldehyde,4,6-dimethoxysalicylaldehyde, 5-methylsalicylaldehyde, 5-bromosalicylaldehyde, 5-nitrosalicylaldehyde, 2,4-dihydroxyben-zaldehyde, 3-tert-butylsalicylaldehyde, 2-hydroxy-1-naphthal-dehyde) in absolute EtOH (20 ml) and heated under reflux for 1 h. Incase of 1b-10b, acetohydroxamic acid (5 mmol) in absolute EtOH(10 ml) was also added with an aldehyde. Then a vanadium(V)oxytriethoxide (5 mmol) in absolute EtOH (10 ml) was added andstirred at room temperature for 2 h. After cooling in a fridge a solid was separated and filtered off, washed several times andrecrystallized from absolute EtOH. 2.4.14 (Acetohydroxamato-κ2O,O'){1S,2R(+)-2-[(1-oxido-1,2-diphenylethyl)iminomethyl]-3,5-dimethoxyphenolato-κ3N,O,O'}oxidovanadium(V) (4b) Yield 80%. Anal. Calc. for C25H25N2O7V: C, 58.1; H, 4.9; N, 5.4. Found: C, 58.2; H, 5.0; N, 5.3%. IR (KBr, cm-1): 3428 (νN-H); 1601, 1573 (νC=O, νC=N); 959 (νV=O). UV-vis spectrum in DMSO [λmax (nm), ɛ (M-1 cm-1)]: 320 (17 850), 489 (3670). CD spectrum in MeOH [λmax (nm), Δɛ (M-1 cm-1)]: 273 (0.24), 322 (-3.95), 371 (3.74), 465 (0.57). 1H NMR (CD3OD, ppm) major (60%): 8.88 (1H, s) (azomethine); 7.51 (2H, dd, 3J = 8 Hz, 4J = 3 Hz), 7.01-7.12 (8H, m), 6.05 (1H, d, 3J = 8 Hz), 5.98 (1H, d, 3J = 8 Hz) (aromatic); 6.47 (1H, d, 3J = 6 Hz), 5.58 (1H, d, 3J = 6 Hz) (methine); 3.84 (3H, s), 3.78 (3H, s) (methoxy); 2.01 (3H, s) (acetyl); minor (40%): 8.83 (1H, s) (azomethine); 7.43 (2H, m), 6.99-7.10 (8H, ov), 6.02 (1H, d, 3J = 8 Hz), 5.97 (1H, ov) (aromatic); 6.71 (1H, d, 3J = 6 Hz), 5.80 (1H, d, 3J = 6 Hz) (methine); 3.87 (3H, s), 3.81 (3H, s) (methoxy); 2.21 (3H, s) (acetyl). 51V NMR (CD3OD, ppm) major (60%): -266.1; minor (40%): -238.4.

Reference： [1]Romanowski, Grzegorz; Kira, Jaromir; Wera, Michał [Journal of Molecular Catalysis A: Chemical, 2014, vol. 381, p. 148 - 160]

32
[ 546-88-3 ]
[ 551-93-9 ]
[ 1837-71-4 ]