25185-95-9|2,6-Dichlorobenzaldehyde oxime| Ambeed

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+

Structure of 25185-95-9

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}

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

Change View

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 25185-95-9 ] Purity: 98% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 25185-95-9 ]

CAS No. :	25185-95-9
Formula :	C₇H₅Cl₂NO
M.W :	190.03
SMILES Code :	ClC1=C(C(Cl)=CC=C1)C=NO
MDL No. :	MFCD00013938

Safety of [ 25185-95-9 ]

GHS Pictogram:
Signal Word:	Danger
Hazard Statements:	H228-H301-H315-H319-H335-H372
Precautionary Statements:	P280-P210-P240-P264-P270-P301+P310-P330-P370+P378-P403+P233-P405-P501
Class:	4.1(6.1)
UN#:	2926
Packing Group:	Ⅲ

Application In Synthesis of [ 25185-95-9 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 25185-95-9 ]

[ 25185-95-9 ] Synthesis Path-Downstream 1~35

1
[ 25185-95-9 ]
[ 1194-65-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	With N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide; triphenylphosphine; In acetonitrile; at 20℃; for 0.166667h;	To the mixture of PPh3 (0.525 g, 2 mmol) and TBBDA (0.287 g, 0.53 mmol) in dry acetonitrile (5 mL), 4-nitrobenzaldehyde oxime (0.166 g, 1 mmol) was added. The mixture was stirred at room temperature. The progress of the reaction was monitored by TLC. After completion of the reaction (Table 1), the solvent was evaporated. The crude products were purified by short-column chromatography (packed with silica gel, using n-hexane/ethyl acetate (8:2) as eluent) to achieve the desired 4-nitrobenzonitrile with 0.13 g, 92% yield.
94%	With (E)-ethyl 2-cyano-2-(2-nitrophenylsulfonyloxyimino)acetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; at 20℃;Inert atmosphere;	General procedure: In an oven-dried two-necked 50 mLround-bottomed flask, equipped with a stirring bar, a solution of the oxime(1.0 mmol) and 2-NO2-C6H4-SO3XY(1.5 mmol) dissolved in anhydrous CH2Cl2 (5.0 mL) wasplaced under the atmosphere of nitrogen. The reaction mixture was stirred atroom temperature for 5 min, then DBU (2.5 mmol) was added drop wise over 2 min.The reaction mixture became a clear homogeneous solution after addition of DBU.The reaction was monitored by TLC. The reaction mixture was diluted with EtOAcand washed with water (2×5 mL) followed by brine (2×5 mL) upon completeconsumption of the starting material. Product was purified by columnchromatography.Furthermore, the by-product Oxymacould be readily recovered by acidifying the aqueous layer, and then extractingwith ethyl acetate. The Oxyma thus recovered can then be reused to regeneratethe sulfonate ester of Oxyma, which can be further used for a separate batch ofreaction.

References: [1]Synthesis,1986,p. 1037 - 1038.
[2]Chinese Chemical Letters,2013,vol. 24,p. 1123 - 1126.
[3]Synthesis,2005,p. 787 - 790.
[4]Tetrahedron Letters,2010,vol. 51,p. 1826 - 1831.
[5]Tetrahedron Letters,2013,vol. 54,p. 4397 - 4400.
[6]Synthetic Communications,1999,vol. 29,p. 2747 - 2752.
[7]Catalysis science and technology,2015,vol. 5,p. 3754 - 3761.
[8]Synthetic Communications,2010,vol. 40,p. 2429 - 2440.
[9]Synthesis,2012,vol. 44,p. 460 - 468.
[10]Synthesis,1992,p. 943 - 944.
[11]Synthetic Communications,1997,vol. 27,p. 1327 - 1333.
[12]Applied Organometallic Chemistry,2015,vol. 29,p. 683 - 689.
[13]European Journal of Inorganic Chemistry,2016,vol. 2016,p. 393 - 402.
[14]Synthetic Communications,2002,vol. 32,p. 2391 - 2394.
[15]Synthetic Communications,2001,vol. 31,p. 1803 - 1807.
[16]Organic Process Research and Development,2017,vol. 21,p. 771 - 778.
[17]Chemical Communications,2015,vol. 51,p. 16346 - 16348.
[18]Bulletin de la Societe Chimique de France,1917,vol. <4> 21,p. 222.
[19]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 4891 - 4899.
[20]Synthesis,2012,vol. 44,p. 377 - 379.
[21]Organic Process Research and Development,2017,vol. 21,p. 771 - 778.

2
[ 83-38-5 ]
[ 25185-95-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	With pyridine; hydroxylamine hydrochloride; at 20℃; for 0.166667h;	Hydroxylamine hydrochloride (6.6 g, 95.0 mmol) was added to a room temperature solution of 2,6-dichlorobenzaldehyde (11.1 g, 63.4 mmol) in pyridine (31.7 mL) giving a mild exotherm. After 10 minutes the excess pyridine was removed in vacuo and the residue was partitioned between Et20 and water. The organic layer was sequentially washed with saturated aqueous NH4CI, brine and the combined aqueous layers were back extracted with several small portions of Et^O. The combined organics extracts were dried over Na2S04, filtered and concentrated in vacuo to give 2,6-dichlorobenzaldehyde oxime (12.4 g, 65.3 mmol, 100% yield) as a white solid. The product was carried on to the next step without further purification. NMR (400MHz, CDCh) δ 8.39 (s, 1H), 7.92 (s, 1H), 7.40-7.36 (m, 2H), 7.27-7.22 (m, 1H).
100%	With pyridine; hydroxylamine hydrochloride; at 20℃; for 0.166667h;	Hydroxylamine hydrochloride (6.6 g, 95 mmol) was added to a room temperature solution of 2,6-dichlorobenzaldehyde (11.1 g, 63.4 mmol) in pyridine (31.7 mL) giving amild exotherm. After 10 minutes the excess pyridine was removed in vacuo and the residue was partitioned between Et20 and water. The organic layer was sequentially washed with saturated aqueous NH4C1, brine and the combined aqueous layers were back extracted with several small portions of Et20. The combined organic extracts were dried over Na2504, filtered and concentrated in vacuo to give 2,6-dichlorobenzaldehyde oxime (12.4 g, 65.3mmol, 100% yield) as a white solid. The product was carried on to the next step without further purification. ‘H NMR (400MHz, CDC13) 8.39 (s, 1H), 7.92 (s, 1H), 7.40-7.36 (m, 2H), 7.27-7.22 (m, 1H).
100%	With pyridine; hydroxylamine hydrochloride; at 20℃; for 0.166667h;	Hydroxylamine hydrochloride (6.6 g, 95 mmol) was added to a room temperature solution of 2,6-dichlorobenzaldehyde (11.1 g, 63.4 mmol) in pyridine (31.7 mL) giving a mild exotherm. After 10 minutes the excess pyridine was removed in vacuo and the residue was partitioned between Et2O and water. The organic layer was sequentially washed with saturated aqueous NH4Cl, brine and the combined aqueous layers were back extracted with several small portions of Et2O. The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo to give a 2,6-dichlorobenzaldehyde oxime (12.4 g, 65.3 mmol, 100% yield) as a white solid. The product was carried on to the next step without further purification. 1H NMR (400 MHz, CDCl3) δ 8.39 (s, 1H), 7.92 (s, 1H), 7.40-7.36 (m, 2H), 7.27-7.22 (m, 1H).

99%	With sodium hydroxide; hydroxylamine hydrochloride; In ethanol; water; at 90℃;Product distribution / selectivity;	Example 32; 6-{4-[5-Cvclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy1-piperidin-l-yl}-l- methyl-1 H-indole-3 -carboxylic acid; <n="56"/>Step l; 2.6-Dichloro-benzaldehyde oxime; Sodium hydroxide 3N (3.14L, 9.43mol) is added dropwise to a stirred suspension of hydroxylamine hydrochloride (675.55g, 9.43mol) in 0.5L of water at O0C. To this mixture is added dropwise a suspension of 2,6-dichlorobenzaldehyde (150Og, 8.57mol) in 7.5L of ethanol and the reaction is heated at 9O0C overnight. The mixture is cooled to room temperature and then, concentrated to dryness. The solid is triturated in a mixture of H2O/EtOH, 10: 1 (4.4L), filtered and dried under high vacuum at 450C overnight. 1621.78g of title compound (99% yield) is obtained as a white solid. MS (m/e): 190 (M+ 1)
98%	With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; at 0 - 90℃; for 24h;	To a solution of NH2OH·HCl (10.9 g, 0.157 mol) in water (100 mL) was added NaOH (6.27 g, 0.157 mol) at 0 C. The resulting solution was then added to a solution of 1 (25.0 g, 0.142 mol) in ethanol (200 mL). The resulting mixture was stirred at 90C for 24 h. The reaction mixture was concentrated under reduced pressure. The solids were collected by filtration and washed with water to give 2 (26.5 g, 98%) as a white compound which was used in the next step without further purification.
98%	With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; at 90℃;	Hydroxylamine hydrochloride (67.6 g, 0.943 mol) was dissolved in 100 mL of water, and sodium hydroxide 3N was added dropwise under stirring at 0 C.(314 mL, 9.43 mol. 2,6-dichlorobenzaldehyde (150 g, 0.857 mol) was added to ethanol (300 mL) to dissolve, and the mixture solution was added dropwise, and then the temperature was raised to 90 C. and stirred overnight.The reaction was monitored by thin layer chromatography (TLC). After the reaction was completed, it was cooled to room temperature and concentrated in vacuo to a 10% solution.The solid was obtained by suction filtration and dried to obtain 162 g of a white solid.Yield: 98%.
97%	With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; at 0 - 90℃;	To a 2 L round-bottom flask containing hydroxylamine hydrochloride (108 g, 1.55mol, 1.3 equiv.), sodium hydroxide (60 g, 1.50 mol, 1.3 equiv.), and water (200 mL) was5 added 2,6-Dichlorobenzaldehyde 1a (200 g, 1.14 mol, 1.0 equiv.) dropwise at 0 C, folov,'edby ethanol (500 mL). The resulting rnixture was heated at 90 C ovemight, and thenconcentrated under reduced pressure. The resulting solids were collected by filtration anddried in an oven tmder reduced pressure, to provide 210 g (97%) of N-[ (2,6-dichlorophenyl)methylidene]-hydroxy lamine l bas an ofi-white solid.
96%	With sodium hydroxide; hydroxylamine hydrochloride; In ethanol; water; at 90℃; for 24h;	A solution of 2, 6-DICHLOROBENZA . DEHYDE (25g, 0.14 mole) in ethanol (200 mL) was added to a solution of HYDROXYLAMINE HYDROCHLORIDE (11G, 0.16 mole) and sodium hydroxide (6.3g, 0.16 mole) in water (100 mL). The resulting mixture was stirred at 90 C for 24 hours. The volume was reduced in vacuo by ca 30 mL which induced a precipitate. The flask was then cooled to room temperature and the white solids were collected by filtration and washed with water (2x 100 ML). Yield = 25.9g. (96%) of 2, 6-DICHLOROBENZALDEHYDE oxime.
96%	With sodium hydroxide; hydroxylamine hydrochloride; In ethanol; water; at 90℃; for 24h;	A solution of 2,6-dichlorobenzaldehyde (25 g, 0.14 mole) in ethanol (200 mL) was added to a solution of hydroxylamine hydrochloride (11 g, 0.16 mole) and sodium hydroxide (6.3 g, 0.16 mole) in water (100 mL). The resulting mixture was stirred at 90° C. for 24 hours. The volume was reduced in vacuo by ca 30 mL which induced a precipitate. The flask was then cooled to room temperature and the white solids were collected by filtration and washed with water (2 100 mL). Yield=25.9 g. (96%) of 2,6-dichlorobenzaldehyde oxime. A 500 mL round bottom flask was charged with a solution of 2,6-dichlorobenzaldehyde oxime (13 g, 0.07 mole) in N,N-dimethyl formamide (150 mL). The flask was placed in an ambient temperature water bath. The flask was then charged with N-chlorosuccinimide (9.2 g, 0.07 mole). Within minutes of dissolution, an exotherm was observed along with a significant color change to dark yellow. The reaction was stirred an additional hour then the contents were then poured into water (200 mL) and the product extracted with diethyl ether (300 mL). The ethereal layer was washed with water (3 100 mL) and brine (50 mL), then dried over anhydrous magnesium sulfate. After filtering, the solvent was removed in vacuo to yield 14.5 g of a yellow oil. (94%) of 2,6-dichlorophenyl hydroximic chloride which was used without further purification. A stirred solution of methyl isobutyryl acetate (2 g, 15.6 mmol) in tetrahydrofuran (15 mL) was treated with a solution of sodium methoxide (31.5 mL, 0.5 M in methanol) followed by a solution of 2,6-dichlorophenyl hydroximic chloride (3.5 g, 15.6 mmol) in tetrahydrofuran (5 mL). After stirring at ambient temp 16 h the solvent was removed in vacuo. The resulting residue was partitioned with diethyl ether (100 mL) and water (100 mL). The ethereal layer was washed with brine (50 mL), dried over anhydrous magnesium sulfate, filtered and condensed to an oil. The product was purified by flash chromatography on silica gel using 10% ethyl acetate in hexane as mobile phase. Yield=3.1 g. (62%) of 3-(2,6-dichlorophenyl)-4-carbomethoxy-5-isopropyl-isoxazole.
96%	With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; at 90℃; for 24h;	A solution of 2,6-dichlorobenzaldehyde A1a (25 g, 0.14 mol) in 200 mL of ethanol was added to a solution of hydroxylamine hydrochloride (11 g, 0.16 mol) and sodium hydroxide (6.3 g, 0.16 mol) in 100 mL of water. The resulting mixture was stirred at 90C for 24 h. The volume was reduced in vacuum by - 30 mL, which induced a precipitate. The flask was then cooled to room temperature and the solid was collected by filtration and washed with water (2 x 100 mL). The solid was dried under vacuum to give 25.9 g of compound A2a (white solid, yield: 96%).
96.5%	With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; at 90℃;	A 3 mol / L sodium hydroxide solution (21 ml, 0.063 mol, 1.1 eq) was added dropwise to a suspension of 3.3 ml of water in hydroxylamine hydrochloride (4.37 g, 0.063 mol, 1.1 eq). The mixed solution was poured into a mixed solution of 50 ml of ethanol and 2,6-dichlorobenzaldehyde (10 g, 0.057 mol, 1.0 eq), and the mixture was heated to 90 C overnight. The reaction solution was concentratedDry, concentrated dry solid was added 29.3 ml (H2O: EtOH = 10: 1) solution, filtered and crystallized,The filter cake was dried and dried in vacuo at 45 C to give intermediate 1-8, 10.48 g as a white solid, 96.5% yield.
96.5%	With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; at 90℃;	At 0 C, 3 mol/L sodium hydroxide solution (21 ml, 0.063 mol, 1.1 eq) was dropped into suspended 3.3 ml waterA solution of hydroxylamine hydrochloride (4.37 g, 0.063 mol, 1.1 eq).The mixed solution was added dropwise to a mixed solution of 50 ml of ethanol and 2,6-dichlorobenzaldehyde (10 g, 0.057 mol, 1.0 eq), and the mixture was heated to 90 C overnight.After the completion of the reaction, the reaction solution was concentrated to dryness, and then concentrated, dried solid was added to a solution of 29.3 ml (H2O:EtOH=10:1).After beating and crystallization, the filter cake was drained and dried under vacuum at 45 C.Intermediate 1-8 was obtained as a white solid 10.48 g, yield 96.5%.
96.5%	With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; at 90℃; for 24h;	Hydroxylamine hydrochloride (10.9g) and sodium hydroxide (6.27g) were dissolved in water at room temperature.Add dropwise to a solution of 2,6-dichlorobenzaldehyde (25 g) in ethanol (200 mL).Stir at 90 degrees for 24 hours.Cool to room temperature,Spin dry ethanol,filter,Wash the filter cake with water,The product was dried under infrared light to obtain 26.5 g of a product.The yield was 96.5%.
96%	With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; at 90℃; for 24h;	Sodium hydroxide(6.3g, 160mmol) and 2,6-dichlorobenzaldehyde(25g, 140mmol) in ethanol(200ml) was added to hydroxylamine hydrochloride(11g, 160mmol) in water(100ml) and stirred for 24 hours at 90 . The reaction mixture was evaporated in vacuum, filtered with water(200ml, 2 times) and dried in vacuum to afford the intermediate compound 2,6-dichlorobenzaldehyde oxime(25.9g, 96%). [585] 1H-NMR (DMSO, 400MHz): δ 11.80 (s, 1H), 8.22 (s, 1H), 7.55 (d, 2H), 7.45-7.41 (dd, 1H).
96%	With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; at 90℃; for 24h;	Hydroxylamine hydrochloride (11 g, 160 mmol) was added to a solution of to distilled water (100 ml) and sodium hydroxide (6.3 g, 160 mmol) and 2,6-Dichlorobenzoaldehyde (25 g, 140 mmol) was added to a solution of Dissolved in ethanol (200 ml) was added, and the mixture was stirred at 90 C for 24 hours.The reaction mixture was concentrated and the resulting solid was washed with distilled water (200 ml, twice) and dried to give the intermediate compound 2,6-dichlorobenzaldehyde oxime (25.9 g, 96%) was obtained.
94%	With hydroxylamine hydrochloride; triethylamine; In dichloromethane; for 8h;Product distribution / selectivity;	Alternate procedure: Add triethylamine (23.1 g, 229 mmol) dropwise to a solution of 2,6-dichloro-benzaldehyde (20.0 g, 114 mmol) and hydroxylamine hydrochloride (10.3 g, 149 mmol) in dichloromethane (200 mL). Stir the reaction mixture for 8 h. Add water (200 mL). Separate the phases and extract the aqueous phase with dichloromethane (100 mL). Wash the combined organic phases with water (100 mL). Concentrate the combined organic phases to provide 28.8 g (94%) of the title compound.
89%	With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; at 90℃;	2,6-dichlorobenzaldehyde (611) (25g,0.14mol) was dissolved in 200mL ethanol, Followed by addition hydroxylamine hydrochloride (0.16 mol)And 6.3 g of sodium hydroxide (0.16 mol) in 100 mL of an aqueous solution.Then the system temperature to 90 C,After the reaction at this temperature for 2-3 h, TLC detection reaction.After the reaction, The solvent was evaporated to about 30 mL, and a large amount of solid was precipitated. The solid was washed with water and dried to give 24 g of product 2,6-dichlorobenzyloxime (AI) (89%).
85%	With pyridine; hydroxylamine hydrochloride; In ethanol; at 0℃;Reflux;	2,6-dichlorobenzaldehyde (25 gm, 0.143 moles, 1 eq) was dissolved in EtOH (200 ml) followed by the addition of hydroxyl amine hydrochloride (19.9 gm, 0.286 moles, 2 eq) and pyridine (34 gm, 0.429 moles, 3 eq) at 00C. The reaction mixture was refluxed for 40 minutes and checked by TLC. The solvent was removed under reduced pressure and to the residue water was added and extracted with ethyl acetate twice. The combined organic layer was washed with brine, dried over Na2SO4, concentrated and washed with chilled hexane to afford the mixture of syn and anti oxime b in 85% yield (23 gm). MS 190.0 (M+ peak) 1H NMR (200 MHz, CDCl3): δ 7.20-7.30 (m, 3H), 7.38-4.00 (m, 3H), 8.20 (s, IH), 8.40 (s, IH) mixture of syn and anti isomers.
85%	With pyridine; hydroxylamine hydrochloride; In ethanol; at 0℃; for 0.666667h;Reflux;	2,6-dichlorobenzaldehyde (25 gm, 0.143 moles, 1 eq) was dissolved in EtOH (200 ml) followed by the addition of hydroxyl amine hydrochloride (19.9 gm, 0.286 moles, 2 eq) and pyridine (34 gm, 0.429 moles, 3 eq) at 00C. The reaction mixture was refluxed for 40 minutes and checked by TLC. The solvent was removed under reduced pressure and to the residue water was added and extracted with ethyl acetate twice. The combined organic layer was washed with brine, dried over Na2SO4, concentrated and washed with chilled hexane to afford the mixture of syn and anti oxime b in 85% yield (23 gm). MS 190.0 (M+ peak) 1H NMR (200 MHz, CDCl3): δ 7.20-7.30 (m, 3H), 7.38-4.00 (m, 3H), 8.20 (s, IH), 8.40 (s, IH) mixture of syn and anti isomers.
78%	With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; at 90℃; for 16h;	3N Sodium hydroxide (8.35 g, 0.208 mol) was added drop wise to a solution of hydroxylamine hydrochloride (l4.5lg, 0.208 mol) in water (130 ml) at 0 C . A solution of 2, 6-dichloro-benzaldehyde (32.0g, 0.182 mol) in ethanol (250 ml) was then added and the reaction mixture heated at 90 C for 16 h. The mixture was then cooled to room temperature, concentrated to dryness and the crude product triturated with 10:1 water/EtOH, filtered and dried under reduced pressure to afford the titled compound as a solid (27.0 g, 78 % yield). 'H NMR (400 MHz, d6-DMSO): d 11.79 (s, 1H), 8.22 (s, 1H), 7.60-7.38 (m, 3H).
64%	With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; at 90℃;	2,6-Dichlorobenzaldehyde (5.0 g, 28.6 mmol) is dissolved in anhydrous ethanol (45 ml), and the mixture is stirred at room temperature, followed by adding NH2OH·HCl (2.3 g, 33.1 mmol), NaOH (1.3 g, 32.5 mmol) and water (20 mL) with overnight reflux in an oil bath at 90 C.When the reaction mixture is cooled to room temperature, the mixture is rotated to remove solvents, followed by adding water (100 mL), and then it is extracted with ethyl acetate (2 * 100 mL), then the organic solution is combined and washed with saturated salt water (2 * 100 mL), and then is dried with anhydrous Na2SO4, then filtered and rotated to dryness, after that, adding petroleum ether (100 mL), and stirring well, finally the product is filtered and dried, so that a white solid, that is 2,6-dichlorobenzaldehyde oxiame, is obtained with a yield of 64%.
	With sodium hydroxide; water; In methanol;	Step 1 2.6-Dichloro-bcnzaldchvdc oximc2,6-Dichloro-benzaldelryde (7.0 g,40 mmol) is added to 10 mL of water and 30 mL of methanol. Sodium hydroxide (4.0 g, 100 mmol) is dissolved in 8 mL of water slowly. The sodium hydroxide solution <n="12"/>is added to the benzaldelαyde solution. The reaction is stirred overnight. The reaction mixture is partitioned between ethyl acetate and water. The organic layer is washed with brine and dried over solid sodium sulfate. The organic layer is filtered and the solvent is removed under reduced pressure to yield the title compound.
	With sodium hydroxide; hydroxylamine hydrochloride; In ethanol; water; at 20℃; for 1h;	BY THE GENERAL PROCEDURE OF R. K. HOWE, ET AL, J. ORG. CHEM., 1980,45, 3916-3918 the aldehyde starting material 245 in 1: 1 ethanol-water was treated with 1.1 equivalents of hydroxylamine hydrochloride and 2.5 equivalents of aqueous sodium hydroxide with cooling. The mixture was then stirred at room temperature for LH. The reaction mixture was extracted with ether, which was discarded and the aqueous layer was separated and acidified to pH 6 with concentrated hydrochloric acid with cooling. The aqueous layer was extracted with ether and the ether layers were separated. The combined ether layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to yield the desired solid oximes.
	With pyridine; hydroxylamine hydrochloride; at 20℃;	Referring to Fig. 3A, the aldehyde starting material 245 was dissolved in pyridine solvent, and 1.0-1. 2 equivalents of solid hydroxylamine hydrochloride was added in one portion and the homogeneous mixture was stirred overnight at room temperature. The mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and this solution was washed with either 1N hydrochloric acid followed by saturated brine, or by saturated brine alone. The ethyl acetate solution was then dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to yield the desired oxime, 247
	With sodium hydroxide; hydroxylamine hydrochloride; In methanol; water;Product distribution / selectivity;	Intermediate Preparation 2; 2,6-Dichloro-benzaldehyde oxime; 2,6-Dichloro-benzaldehyde (7.0 g, 40 mmol) and hydroxylamine hydrochloride (2.16 g, 44 mmol) are added to 10 mL of water and 30 mL of methanol. Sodium hydroxide (4.0 g, 100 mmol) is dissolved in 8 mL of water slowly. The sodium hydroxide solution is added to the benzaldehyde solution. The reaction is stirred overnight. The reaction mixture is partitioned between ethyl acetate and water. The organic layer is washed with brine and dried over solid sodium sulfate. The organic layer is filtered and the solvent is removed under reduced pressure to yield the title compound.
	With hydroxylamine hydrochloride; In water; at 20℃; for 0.5h;Green chemistry;	General procedure: The aqueous solution of hydroxylamine hydrochloride (1.2 mmol) and aldehyde 2 (1 mmol) were stirred at room temperature for 30 min. After complete conversion of aldehyde to oxime, N-chlorosuccinamide (1.3 mmol) was added to the reaction mixture and was allowed to stir for 3 h. The clay-Cu(II)/NaN3 mixture (prepared by stirring 15 mol % clay-Cu catalyst and 7.5 mol % NaN3 in water until the color changes from brown to black) and phenyl acetylene 5a (1.3 mmol) was added and the reaction mixture was further stirred for another 3 h. After completion of reaction, the reaction mixture was filtered through Whatman filter paper, residue was washed with EtOAc. Organic layer was separated from filtrate and was dried over anhydrous sodium sulfate. Combined organic layers were concentrated in vacuo and crude reaction mixture was purified by silica gel (100-200) column chromatography using EtOAc: hexane as eluting solvent to get corresponding 3,5-disubstituted isoxazoles 1a-1o in 68-88% yield.
	With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; at 0 - 90℃;	To a 2 L round-bottom flask containing hydroxylamine hydrochloride (108 g, 1.55 mol, 1.3 equiv.), sodium hydroxide (60 g, 1.50 mol, 1.3 equiv.), and water (200 mL) was added 2,6- dichlorobenzaldehyde la (200 g, 1 .14 mol, 1.0 equiv,), followed by ethanol (500 mL) at 0 C. The resulting mixture was stirred at 90 C overnight and then concentrated in vacuo. The resulting solids were collected by filtration and dried in an oven under reduced pressure, providing N-[(2,6-dichlorophenyl)methylidene]-hydroxylamine lb (210 g, 97%) as an off-white solid. The product was carried onto the next step without further purification.
	With hydroxylamine hydrochloride; sodium hydroxide; In water; at 83℃; for 3h;pH < 9.5;	A solution of hydroxylamine hydrochloride (0.25 M) was prepared and sufficient quantity of water was added in order to keep the pH of solution below 2.5 and temperature of the solution below 25C. To this solution NaOH was added in order to keep the temperature below 50C and pH of the solution below 9.5. To this warm solution was slowly added 2,6-dichlorobenzaldehyde by keeping temperature below 83C. When addition of aldehyde was over, crystalline product formation was observed within 2-3 minutes. Reaction progress was monitored by TLC. Reaction was completed within 3 hours. Reaction mass was filtered and was dried in oven to obtain crystalline 2,6-dichlorobenzaldehyde oxime of formula VIII.

References: [1]Chemical Communications,2003,p. 1936 - 1937.
[2]Patent: WO2019/89664,2019,A1 .Location in patent: Page/Page column 66.
[3]Patent: WO2019/89670,2019,A1 .Location in patent: Page/Page column 54.
[4]Patent: US2019/127362,2019,A1 .Location in patent: Paragraph 0396-0397.
[5]Patent: WO2009/12125,2009,A1 .Location in patent: Page/Page column 54-55; 67-68.
[6]Journal of Medicinal Chemistry,2015,vol. 58,p. 9768 - 9772.
[7]Journal of Medicinal Chemistry,2020,vol. 63,p. 12748 - 12772.
[8]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 3726 - 3730.
[9]Patent: CN110452235,2019,A .Location in patent: Paragraph 0159; 0161-0163.
[10]Letters in drug design and discovery,2020,vol. 17,p. 12 - 20.
[11]Chemical Biology and Drug Design,2015,vol. 86,p. 637 - 647.
[12]Patent: WO2018/39386,2018,A1 .Location in patent: Page/Page column 142.
[13]Journal of Medicinal Chemistry,2000,vol. 43,p. 2971 - 2974.
[14]Patent: WO2004/48349,2004,A1 .Location in patent: Page 45; 46.
[15]Patent: US6639078,2003,B1 .Location in patent: Page/Page column 14-15.
[16]Patent: WO2011/20615,2011,A1 .Location in patent: Page/Page column 34.
[17]Patent: CN106632294,2017,A .Location in patent: Paragraph 0090; 0092; 0093; 0094.
[18]Patent: CN108218852,2018,A .Location in patent: Paragraph 0144; 0145; 0146; 0147.
[19]Patent: CN108264506,2018,A .Location in patent: Paragraph 0022; 0038-0040.
[20]Patent: WO2018/190643,2018,A1 .Location in patent: Paragraph 582-585.
[21]Patent: KR2018/115126,2018,A .Location in patent: Paragraph 0108; 0236-0238.
[22]Patent: WO2009/12125,2009,A1 .Location in patent: Page/Page column 55.
[23]Journal of Medicinal Chemistry,2020,vol. 63,p. 8369 - 8379.
[24]Patent: CN104341316,2017,B .Location in patent: Paragraph 0293; 0296; 0297.
[25]Patent: WO2010/104929,2010,A1 .Location in patent: Page/Page column 58-59.
[26]Patent: WO2010/104967,2010,A1 .Location in patent: Page/Page column 58-59.
[27]European Journal of Organic Chemistry,2014,vol. 2014,p. 4536 - 4547.
[28]Patent: WO2020/33382,2020,A1 .Location in patent: Page/Page column 35.
[29]Patent: EP3401315,2018,A1 .Location in patent: Paragraph 0047; 0048; 0049.
[30]ChemMedChem,2020,vol. 15,p. 50 - 67.
[31]Justus Liebigs Annalen der Chemie,1932,vol. 495,p. 249,275.
[32]Bulletin de la Societe Chimique de France,1917,vol. <4> 21,p. 222.
[33]Synthetic Communications,2001,vol. 31,p. 3151 - 3159.
[34]Synthesis,2005,p. 787 - 790.
[35]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 4891 - 4899.
[36]Patent: WO2007/92751,2007,A2 .Location in patent: Page/Page column 10-11.
[37]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 5209 - 5212.
[38]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 2969 - 2973.
[39]Patent: WO2004/99164,2004,A1 .Location in patent: Page 42-43; 6/22; 9/22.
[40]Patent: WO2004/99164,2004,A1 .Location in patent: Page 42; 6/22; 9/22.
[41]Patent: WO2009/12125,2009,A1 .Location in patent: Page/Page column 17.
[42]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 1617 - 1625.
[43]Journal of Heterocyclic Chemistry,2012,vol. 49,p. 621 - 627.
[44]Organometallics,2012,vol. 31,p. 6482 - 6490.
[45]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 1482 - 1485.
[46]Tetrahedron Letters,2013,vol. 54,p. 3558 - 3561.
[47]European Journal of Medicinal Chemistry,2014,vol. 87,p. 71 - 78.
[48]Journal of Medicinal Chemistry,2017,vol. 60,p. 9960 - 9973.
[49]Angewandte Chemie - International Edition,2018,vol. 57,p. 9456 - 9460.
Angew. Chem.,2018,vol. 130,p. 9600 - 9604,5.
[50]Archiv der Pharmazie,2019,vol. 352.
[51]Patent: WO2018/39384,2018,A1 .Location in patent: Paragraph 00347.
[52]Advanced Synthesis and Catalysis,2020,vol. 362,p. 5794 - 5800.
[53]Patent: WO2020/249064,2020,A1 .Location in patent: Paragraph 000140; 000148; 000149.
[54]Patent: WO2021/117053,2021,A1 .Location in patent: Page/Page column 18-19.
[55]Organic Letters,2021,vol. 23,p. 5750 - 5754.
[56]ACS Medicinal Chemistry Letters,2021,vol. 12,p. 1413 - 1420.
[57]Chemical Biology and Drug Design,2022,vol. 99,p. 483 - 495.

3
[ 25185-95-9 ]
[ 6579-27-7 ]

Yield	Reaction Conditions	Operation in experiment
97.7%	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 40℃; for 1h;	2,6-dichlorobenzanamine (10.48 g, 0.055 mol, 1.0 eq) was dissolved in 63 ml of DMF and N-chlorosuccinimide (7.36 g, 0.28 mol, 1.0 eq) was added portionwise.And the mixture was stirred at 40 C for 1 h. The reaction solution was finished and cooled to a temperature,Poured into 200 ml of ice water at 0 C, extracted with 200 ml of methyl tert-butyl ether, and the aqueous layer was discarded. The organic layer was washed with brine, dried over anhydrous sodium sulfate, evaporated to dryness at 30 C to form a solid oil. The crystals were triturated with 6 ml of n-hexane to form a solid filter. The filter cake was dried in vacuo to give intermediate 8-1-2,Yellow solid 12.10 g,the yield was 97.7%.
97.7%	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 40℃; for 1h;	2,6-dichlorobenzylhydroxylamine (10.48 g, 0.055 mol, 1.0 eq) was dissolved in 63 ml N-chlorosuccinimide (7.36 g, 0.28 mol, 1.0 eq) was added portionwise in DMF. After the addition, the mixture was stirred at 40 C for 1 h. The reaction mixture was completed, cooled to room temperature, poured into 200 ml of ice water at 0 C, extracted once with 200 ml of methyl tert-butyl ether, and the aqueous layer was discarded.The organic layer was washed with brine, dried over anhydrous sodium sulfate and evaporated to drynessThe filter cake was vacuum dried to give Intermediate 8-1-2, 12.10 g of a yellow solid, yield 97.7%.
97%	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 20℃; for 1h;	2,6-Dichlorobenzaldehyde oxime (26 g) was dissolved in DMF (160 mL).Add NCS (18.5g) in portions at room temperature.After stirring for 1 hour,Pour the solution into water (800 mL),Extracted with ethyl acetate,The ethyl acetate layers were combined and washed with water and saturated brine, respectively.Dry with anhydrous sodium sulfate,The solvent was added to dryness to give 30 g, m.

97%	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 25℃; for 1h;	To a solution of 2 (26.0 g, 0.138 mol) in DMF (160 mL) was slowly added NCS (18.5 g, 0.139 mol) and kept the internal temperature below 25 C. The reaction mixture was stirred for 1 h at room temperature, then poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 3 (30.0 g, 97%) as light yellow oil which was used in the next step without further purification.
96%	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 20℃; for 2h;	To aIL round-bottom flask was addedN-[(2,6-dichlorophenyl) methylidene]hydroxylanrine lb (60 g, 315.74 mmol, 1.0 equiv.), N.N-dimethylformamide (250 mL), andN-chlorosuccinimide (NCS, 42.5 g, 318.28 mmol, 1.0 equiv.). The resulting nrixture was stirred for 2 h at room temperature, and then quenched by the addition of 500 mL of ice/salt.The aqueous mixture was extracted v.ith ethyl acetate (lL x 3) and the combined organiclayers were washed with brine (l L x 3), dried vvith sodium sulfate, filtered and concentratedin vacuo to give result 68 g (96%) of 2,6-dichloro-N-hydroxylbenzene-l-carbonimidoyl5 chloride J c as a white solid.
94%	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 20℃; for 1h;	A solution of 2,6-dichlorobenzaldehyde (25 g, 0.14 mole) in ethanol (200 mL) was added to a solution of hydroxylamine hydrochloride (11 g, 0.16 mole) and sodium hydroxide (6.3 g, 0.16 mole) in water (100 mL). The resulting mixture was stirred at 90° C. for 24 hours. The volume was reduced in vacuo by ca 30 mL which induced a precipitate. The flask was then cooled to room temperature and the white solids were collected by filtration and washed with water (2 100 mL). Yield=25.9 g. (96%) of <strong>[25185-95-9]2,6-dichlorobenzaldehyde oxime</strong>. A 500 mL round bottom flask was charged with a solution of <strong>[25185-95-9]2,6-dichlorobenzaldehyde oxime</strong> (13 g, 0.07 mole) in N,N-dimethyl formamide (150 mL). The flask was placed in an ambient temperature water bath. The flask was then charged with N-chlorosuccinimide (9.2 g, 0.07 mole). Within minutes of dissolution, an exotherm was observed along with a significant color change to dark yellow. The reaction was stirred an additional hour then the contents were then poured into water (200 mL) and the product extracted with diethyl ether (300 mL). The ethereal layer was washed with water (3 100 mL) and brine (50 mL), then dried over anhydrous magnesium sulfate. After filtering, the solvent was removed in vacuo to yield 14.5 g of a yellow oil. (94%) of 2,6-dichlorophenyl hydroximic chloride which was used without further purification. A stirred solution of methyl isobutyryl acetate (2 g, 15.6 mmol) in tetrahydrofuran (15 mL) was treated with a solution of sodium methoxide (31.5 mL, 0.5 M in methanol) followed by a solution of 2,6-dichlorophenyl hydroximic chloride (3.5 g, 15.6 mmol) in tetrahydrofuran (5 mL). After stirring at ambient temp 16 h the solvent was removed in vacuo. The resulting residue was partitioned with diethyl ether (100 mL) and water (100 mL). The ethereal layer was washed with brine (50 mL), dried over anhydrous magnesium sulfate, filtered and condensed to an oil. The product was purified by flash chromatography on silica gel using 10% ethyl acetate in hexane as mobile phase. Yield=3.1 g. (62%) of 3-(2,6-dichlorophenyl)-4-carbomethoxy-5-isopropyl-isoxazole.
94%	With N-chloro-succinimide; N,N-dimethyl-formamide; at 40℃;	2,6-Dichlorobenzaldehyde oxime (12.0 g, 63.1 mmol) was dissolved in DMF (45.9 mL) and heated to 40 C. NCS (10.1 g, 76.0 mmol) dissolved in DMF (38.3 mL) was then added to the warm solution over the space of approximately 3 minutes. After stirring overnight the reaction mixture was cooled to room temperature, poured into ice, and extracted with Et^O. The organic layer was collected and washed with brine. The combined aqueous layers were back extracted with Et20. The combined organic layers were dried over Na2S04, filtered and concentrated to dryness in vacuo. The residue was purified by flash chromatography on SiC (0-50% EtOAc/hexanes, Isco 120 g column) to give 2,6- dichloro-N-hydroxybenzimidoyl chloride (13.3 g, 59.3 mmol, 94% yield) as a waxy white solid. NMR (500 MHz, CDCh) δ 8.02 (s, 1H), 7.43-7.37 (m, 2H), 7.37-7.30 (m, 1H).
94%	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 40℃;	2,6-Dichlorobenzaldehyde oxime (12.0 g, 63.1 mmol) was dissolved in DMF (45.9 mL) and heated to 40 C. NCS (10.1 g, 76.0 mmol) dissolved in DMF (38.3 mL) was added to the warm solution over the space of approximately 3 minutes. After stirring overnight the reaction mixture was cooled to room temperature, poured into ice, and extracted with Et20. The organic layer was collected and washed with brine. The combined aqueous layers were back extracted with Et20. The combined organic layers were dried over Na2SO4, filtered and concentrated to dryness in vacuo. The residue was purified by flash chromatography on Si02 (0-50% EtOAc/hexanes, Isco 120 g column) to give 2,6-dichloro-N-hydroxybenzimidoyl chloride (13.3 g, 59.3 mmol, 94% yield) as a waxy white solid. ‘H NMR (500 MI-Tz, CDC13) ö 8.02 (s, 1H), 7.43-7.37 (m, 2H), 7.37-7.30 (m, 1H).
94%	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 40℃;	2,6-Dichlorobenzaldehyde oxime (12.0 g, 63.1 mmol) was dissolved in DMF (45.9 mL) and heated to 40C. NCS (10.1 g, 76.0 mmol) dissolved in DMF (38.3 mL) was then added to the warm solution over the space of approximately 3 minutes. After stirring overnight at 40C. the reaction mixture was cooled to room temperature, poured into ice, and extracted with Et2O. The organic layer was collected and washed with brine. The combined aqueous layers were back extracted with Et2O. The combined organic layers were dried over Na2SO4, filtered and concentrated to dryness in vacuo. The residue was purified by flash chromatography on SiO2 (0-50% EtOAc/hexanes, Isco 120 g column) to give 2,6-dichloro-N-hydroxybenzimidoyl chloride (13.3 g, 59.3 mmol, 94% yield) as a waxy white solid. 1H NMR (500 MHz, CDCl3) δ 8.02 (s, 1H), 7.43-7.37 (m, 2H), 7.37-7.30 (m, 1H).
90%	With N-chloro-succinimide; In N,N-dimethyl-formamide; for 2h;	N-chlorosuccinimide (19.06 g, 0.1428 mol) was added portion wise to a solution of 2, 6-dichlorobenzaldehyde oxime (27 g, 0.1428 mole) in DMF (300 ml). After 2h the reaction was poured into water and the product extracted with ethyl acetate. The combined organic layers were washed with water, brine and dried over anhydrous sodium sulfate. After filtering, the solvent was removed under reduced pressure to afford the titled compound as yellow oil (29 g, 90 %). 1H NMR (400 MHz, d6-DMSO): d 12.68 (s, 1H), 7.72-7.52 (m, 3H).
80%	With N-chloro-succinimide; In N,N-dimethyl-formamide;	Take 2,6-dichlorobenzyloxime 13g (70 mmol) in 250 mL two bottles,Add 150 mL of DMF dissolved,Then 9.2 g NCS (70 mmol) was added in portions.Plus finished, continue to respond 2-3h,TLC showed complete reaction.The system was then added to 200 mL of ice water,There will be needle-like solid production,Ethyl acetate was added,Saturated sodium chloride wash,Dried over anhydrous sodium sulfate to give about 12 g of product 2,6_dichlorobenzyloxymethoxime (80%)
75%	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 40 - 45℃; for 3.5 - 7h;Product distribution / selectivity;	Step 2; 2,6-Dichloro-benzaldehyde chloro-oxime; <n="57"/>N-Chlorosuccinimide (1162g, 8.53mol) in DMF (4.5L) is added dropwise over a solution of 2,6-dichloro-benzaldehyde oxime (1621.78g, 8.53mol) in DMF (5.3L) heated at 4O0C (addition is complete in about 6 hours). The mixture is stirred for Ih at that temperature. The reaction is cooled at room temperature, poured onto H2O (30L) at O0C, and extracted with MTBE (36L) and the aqueous phase was discarded. The organic layer is washed with brine, dried over Na2SO4, filtered and evaporated to dryness (at 3O0C). The crude, as a solid-oil, is triturated in IL of hexane and the solid formed is filtered and dried under vacuum to obtain the desired compound (1440.9g, 75% yield). MS (m/e): 224 (M+l). Alternate Procedure: Add a solution of N-chlorosuccinimide (8.4 g, 62.8 mmol) in DMF (33 mL) to a 42 0C solution of 2,6-dichloro-benzaldehyde oxime (217 g, 1.14 mol) in DMF (700 mL). Stir for 30 minutes and then add a solution of N- chlorosuccinimide (159 g, 1.19 mol) in DMF (617 mL) while maintaining the temperature between 40 0C and 45 0C. Stir for 1 hour. Cool to room temperature and stir for 2 h. The resulting solution of the title compound is used directly
	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 5 - 20℃; for 1 - 1.33333h;Product distribution / selectivity;	6b) Ethyl 5-cyclopentyl-3-(2,6-dichlorophenyl)-4-isoxazolecarboxylate To a solution of <strong>[25185-95-9]2,6-dichlorobenzaldehyde oxime</strong> (3.73 g, 19.6 mmol) in N,N-dimethylformamide (12 mL) was added solid N-chlorosuccinimide (2.62 g, 19.6 mmol). The solution was stirred for approximately 1 hour and the poured into water and extracted twice with ether. The combined organic layers containing the crude imidoyl chloride were dried over magnesium sulfate and concentrated. To a solution of ethyl 3-cyclopentyl-3-oxopropanoate (4.34 g, 23.6 mmol) in tetrahydrofuran (5 mL) at 0 C. was added a 25 wt % solution of sodium ethoxide in ethanol (7.4 mL, 24 mmol) quickly. The above imidoyl chloride was added. A solid was seen to precipitate. The mixture was allowed to warm to ambient temperature and stir overnight. The mixture was then poured into water and extracted three times with ethyl acetate and the combined organic layers were dried over magnesium sulfate, concentrated and the residue purified by chromatography (silica gel 5% ethyl acetate in hexanes) to afford ethyl 5-cyclopentyl-3-(2,6-dichlorophenyl)-4-isoxazolecarboxylate (3.04 g, 43%). 1H-NMR (400 MHz, DMSO-d6) δ 7.63-7.53 (m, 3H), 4.02 (q, J=7 Hz, 2H), 3.92-3.84 (m, 1H), 2.14-2.06 (m, 2H), 1.84-1.64 (m, 6H), 0.91 (t, J=5 Hz, 3H).; 7a) Ethyl 5-cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolecarboxylate To a water bath-cooled solution of <strong>[25185-95-9]2,6-dichlorobenzaldehyde oxime</strong> (2.20 g, 11.6 mmol) in N,N-dimethylformamide (7 mL) was added solid N-chlorosuccinimide (1.55 g, 11.6 mmol). The solution was stirred while in the water bath for approximately 20 min and outside the bath for approximately 1 hr. The solution was poured into water and extracted twice with ether. The combined organic layers containing the crude imidoyl chloride were dried over magnesium sulfate and then concentrated. To a separate solution of ethyl 3-cyclobutyl-3-oxopropanoate (2.37 g, 13.9 mmol) in THF (3 mL) at 0 C. was added sodium ethoxide (25 wt % in ethanol, 4.36 mL, 13.9 mmol). The solution was stirred for a few minutes and then the above imidoyl chloride was added. The solution was stirred at 0 C. for 10 minutes and then at ambient temperature overnight. The solution was poured into water and extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, concentrated and purified by chromatography (silica gel, 0-5% ethyl acetate in hexanes gradient elution) to afford ethyl 5-cyclobutyl-3-(2,6-dichlorophenyl)-4-isoxazolecarboxylate (1.52 g, 38%). 1H-NMR (400 MHz, DMSO-d6) δ 7.63-7.53 (m, 3H), 4.29-4.20 (m, 1H), 4.02 (q, J=7 Hz, 2H), 2.43-2.36 (m, 4H), 2.15-2.06 (m, 1H), 1.97-1.89 (m, 1H), 0.94 (t, J=7 Hz, 3H).10b) Ethyl 5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolecarboxylate To a water bath-cooled solution of <strong>[25185-95-9]2,6-dichlorobenzaldehyde oxime</strong> (2.20 g, 11.6 mmol) in N,N-dimethylformamide (7 mL) was added solid N-chlorosuccinimide (1.55 g, 11.6 mmol). The solutions were stirred while in the water bath for approximately 20 min and the outside the bath for approximately 1 hour. The solution was poured into water and extracted twice with ether. The combined organic layers containing the crude imidoyl chloride were dried over magnesium sulfate and then concentrated. To a separate solution of ethyl 3-cyclopropyl-3-oxopropanoate (2.17 g, 13.9 mmol) in THF (3 mL) at 0 C. was added sodium ethoxide (25 wt % in ethanol, 4.36 mL, 13.9 mmol). The solution was stirred for a few minutes and then the above imidoyl chloride was added. The solution was stirred at 0 C. for 10 minutes and then at ambient temperature overnight. The solution was poured into water and extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, concentrated and purified by chromatography (silica gel, 0-5% ethyl acetate in hexanes gradient elution) to afford ethyl 5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolecarboxylate (289 mg, 8%). 1H-NMR (400 MHz, DMSO-d6) δ 7.62-7.53 (m, 3H), 4.04 (q, J=7 Hz, 2H), 2.84-2.82 (m, 1H), 1.35-1.25 (m, 4H), 0.93 (t, J=7 Hz, 3H).; 13b) {3-(2,6-Dichlorophenyl)-5-[(1S)-1-methylpropyl]-4-isoxazolyl}methanol To a solution of <strong>[25185-95-9]2,6-dichlorobenzaldehyde oxime</strong> (26.4 g, 139 mmol) in N,N-dimethylformamide (70 mL) at 5 C. was added solid N-chlorosuccinimide (18.6 g, 139 mmol) in portions. The mixture was allowed to stir and warm to ambient temperature (with occasional cooling when warming was noted) over approximately 1.5 hour and then poured into ether. The ether layer containing the crude imidoyl chloride was washed twice with water followed by brine, dried over magnesium sulfate and concentrated. To a separate solution of ethyl 4-methyl-3-oxohexanoate (28.8 g, 167 mmol) in tetrahydrofuran (50 mL) at 0 C. was added sodium ethoxide (21 wt % in ethanol, 62.3 mL, 167 mmol) quickly. Then the above imidoyl chloride was added dropwise in tetrahydrofuran (100 mL). The solution was allowed to stir while warming to ambient temperature overnight. The mixtur...
	With N-chloro-succinimide; In DMF (N,N-dimethyl-formamide); at 20℃;	A solution of 2, 6-DICHLOROBENZALDEHYDE oxime (19. 8g, 0.104 mol) in N, N-dimethyl formamide (80 mL) was placed in an ambient temperature water bath and was treated with N-CHLOROSUCCINIMIDE (13.9g, 0.104 mole). Following dissolution, an exotherm was observed along with a color change to dark yellow. The reaction was stirred an additional hour then the contents were then poured into water (200 mL) and the product extracted with diethyl ether (300mL). The ethereal layer was washed with water (3x 100 mL) and brine (50mL), then dried over anhydrous magnesium sulfate. After filtering, the solvent was removed in vacuo to yield a yellow oil which was used in the next step without further purification. Separately, a solution of methyl isobutyryl acetate (18g, 0.125 mol) in tetrahydrofuran (25 mL) at 0C was treated with a solution of sodium methoxide (250 mL, 0.5 M in methanol). A solution of the above crude 2, 6-DICHLORO-N-HYDROXYBENZENECARBOXIMIDOYL chloride in tetrahydrofuran (80 mL) was then added dropwise. After stirring at ambient temperature for 16h the solvent was removed in vacuo. The residue was triturated with water (250 mL) and the resulting solids filtered and washed with water. Yield = 22.7 g. (69%) of methyl 3- (2, 6-dichlorophenyl)-5-isopropylisoxazole-4-carboxylate.
	With N-chloro-succinimide; In DMF (N,N-dimethyl-formamide); at 40 - 50℃; for 0.5h;	THE GENERAL PROCEDURE OF R. K. HOWE ET AL, J. ORS. CHEM., 1980, 45,3916-3918 WAS followed. 2,6-Dichlorobenzaldoxime (25.1 gm, 0.132 mol) was dissolved in DMF (150 mL). Then N-chlorosuccinimide (approximately 1.5 g) was added. After several minutes the reaction was heated until the internal temperature reached 50 C. Then the remainder of the N-chlorosuccinimide was added in small portions to a total of 17.6 g (0.132 mol), keeping the reaction temperature at 40-50 C. After the addition was complete, the reaction was allowed to stir for 0. 5H, then was diluted with 600 mL of water. The mixture was extracted twice with ether. The combined ether extracts were washed three times with water, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was concentrated under vacuum to give the title a-chlorooxime as a white solid (m. p. 89-90 C). NMR (300 MHz, CDC13) : 7.98 (s, 1H, exchanges with D20), 7.3-7. 4 ppm (m, 3H).Again referring to FIG. 3A, the general procedure described by R. K. Howe, et al, J. P ORG. CHEM., 1980,45, 3916-3918 WAS FOLLOWED. THE OXIME WAS DISSOLVED IN DMF AND 0.1 molar equivalent of N-chlorosuccinimide was added and the mixture was heated to 50 C to initiate the reaction. The remaining 0.9 molar equivalent of N-CHLOROSUCCINIMIDE was added in small portions keeping the reaction temperature under 50 C. After the addition was completed, the mixture was stirred for 0. 5h and then diluted with water. The mixture was extracted with ether and the combined ether extracts were washed with water and brine. The ether layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to yield the desired α-chlorooxime 247
	With hydrogenchloride; N-chloro-succinimide; In N,N-dimethyl-formamide;Product distribution / selectivity;	Intermediate Preparation 3; 2,5 Dichlorobenzaldehyde-chloro-oxime; 2,6-Dichloro-benzaldehyde oxime (7.6 g, 40 mmol) is dissolved in 56 mL of DMF and N-chlorosuccinimide (5.9 g, 44.0 mmol) is added followed by a catalytic amount of HCl gas. The reaction mixture is stirred overnight. The reaction mixture is partitioned between ether and water. The layers are separated and the ether layer is washed with brine and is dried over sodium sulfate. The ether layer is filtered and the solvent is removed under reduced pressure to yield the crude product. The crude product is purified via chromatography using a gradient of 10 % ethyl acetate in hexanes to 15% ethyl acetate in hexanes to yield the title compound. 1H-NMR (400MHz, CDCl3) δ 8.76 (broad, IH), 7.38-7.26 (m,3H)
	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 20℃; for 1h;	A 500 mL round bottom flask was charged with a solution of compound A2a (25.9 g, 0.14 mol) in 300 ml_ of DMF. The flask was placed in an ambient temperature water bath. The flask was then charged with NCS (18.4 g, 0.14 mol). The reaction was stirred an additional hour, then the contents was poured into 400 mL of water and the product was extracted with 500 mL of Et2O. The organic layer was washed with water (2 x 200 mL) and 100 mL of brine, then dried over MgSO4. After filtration, the solvent was removed under reduced pressure to give 29 g of compound A3a as a yellow oil which was used into the following reaction without further purification.
	With hydrogenchloride; N-chloro-succinimide; In dichloromethane; water; at 20℃; for 4h;	General procedure: To a stirred solution of oxime (1.3 mmol) in CH2Cl2 (10 mL) (or in DMF for pyridine-2-carboxaldoxime) at room temperature was added solid NCS (0.187 g, 1.4 mmol). The reaction was initiated by the addition of one drop of concd hydrochloric acid. After stirring for 4 h, the solution of hydroximoyl chloride in CH2Cl2 (or in DMF) was used in the cycloaddition. Yield >98%.
26 g	With N-chloro-succinimide; In chloroform; at 20℃; for 4h;	N-chlorosuccinimide(NCS, 18.4g, 140mmol) was added to a solution of the intermediate compound(Step 1)(25.9g, 140mmol) in chloroform(1000ml) and stirred for 4 hours at room temperature. The reaction mixture was evaporated in vacuum, diluted with dicholrometane and washed with water. The combined organic layers were dried over MgSO 4, filtered, evaporated in vacuum and purified using silica chromatography to afford the intermediate compound 2,6-dichloro-N-hydroxybenzimidoyl chloride(29g) without any further purification
5.5 g	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 20℃; for 1h;	2,6-Dichlorobenzaldehyde oxime (4.7 g, 24.7 mmol) is dissolved in DMF (40 mL), followed by adding NCS (3.3 g, 24.7 mmol), and the mixture is stirred at room temperature for 1 hr. After that, water (100 mL) is poured into the reaction mixture, and then the mixture is extracted with diethyl ether (2 * 150 mL), the organic solution is combined and washed with saturated salt water (3 * 100 mL), followed by adding anhydrous Na2SO4 for drying , and subsequently the resulted product is filtered and rotated to dryness. Finally, 5.5 g of yellow oily matter, 2,6-dichloro-N-hydroxybenzimidoyl chloride is obtained and it is directly used in the next step without purification.
	With N-chloro-succinimide; In chloroform; at 20℃; for 4h;	The intermediate compound (25.9 g, 140 mmol) prepared in the above step 1 was dissolved in chloroform (1000 ml)N-chlorosuccinimide (NCS, 18.4 g, 140 mmol) was added thereto, followed by stirring at room temperature for 4 hours.The reaction mixture was concentrated, diluted with dichloromethane and washed with distilled water.Dried with magnesium sulfate, Filtration and concentration afforded the intermediate compoundTo give 2,6-dichloro-N-hydroxybenzimidoyl chloride (29 g)Was used in the next reaction without further purification.
	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 20℃; for 2h;	To a 1 L round-bottom flask was added N-[(2,6-dichlorophenyl) methylidene]hydroxylamine lb (60 g, 3 15.74 mmol, 1.0 equiv.), N,N-dimethylformamide (250 mL), and N-chl orosucci nimide (42.5 g, 318.28 mmol, 1.0 equiv.). The resulting mixture was stirred for 2 h at RT and then quenched by with ice/brine (500 mL). The aqueous mixture was extracted with EtOAc (1 L x 3), The combined organic layers were washed with brine ( 1 L x 3), and concentrated in vacuo to give 2,6-dichloro-N-hydroxylbenzene-l-carbonimidoyl chloride lc (68 g, 96%) as a white solid. The product was carried onto the next step without further purification.
88.6 g	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 40℃; for 1h;	2,6-Dichloro-benzaldehyde oxime (100g, 0.526mol) was dissolved in DMF (N, N-dimethylformamide, 200mL),willChlorosuccinimide (70.3 g, 0.526 mol) was dissolved in 100 mL of DMF and dropped into the above 2,6-dichloro-benzaldehyde oxime solution at 40 C, and then reacted at 40 C for 1 hour.The reaction was monitored by thin layer chromatography (TLC). After the reaction was completed, the reaction was cooled to room temperature, and a large amount of water and ethyl acetate (EA) were added for extraction.The organic layer was washed three times with 200 mL of water, and the organic layer was washed with 200 mL of saturated saline, dried over anhydrous Na2SO4, and the organic layer was spin-dried.A crude product was obtained, and 100 ml of hexane was added for grinding, suction filtration, and drying.88.6 g of a solid was obtained as 2,6-dichloro-benzaldehyde-chloro-oxime.

References: [1]Journal of Organic Chemistry,1992,vol. 57,p. 6649 - 6650.
[2]ChemMedChem,2020,vol. 15,p. 50 - 67.
[3]Patent: CN106632294,2017,A .Location in patent: Paragraph 0090; 0095; 0096; 0097.
[4]Patent: CN108218852,2018,A .Location in patent: Paragraph 0144; 0148; 0149; 0150.
[5]Patent: CN108264506,2018,A .Location in patent: Paragraph 0022; 0041-0043.
[6]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 3726 - 3730.
[7]Journal of Chemical Research,2007,p. 26 - 28.
[8]Patent: WO2018/39386,2018,A1 .Location in patent: Paragraph 142; 143.
[9]Journal of Medicinal Chemistry,2020,vol. 63,p. 8369 - 8379.
[10]European Journal of Organic Chemistry,2014,vol. 2014,p. 4536 - 4547.
[11]Journal of Medicinal Chemistry,2020,vol. 63,p. 12748 - 12772.
[12]Patent: US6639078,2003,B1 .Location in patent: Page/Page column 15.
[13]Patent: WO2019/89664,2019,A1 .Location in patent: Page/Page column 66; 67.
[14]Patent: WO2019/89670,2019,A1 .Location in patent: Page/Page column 54; 55.
[15]Patent: US2019/127362,2019,A1 .Location in patent: Paragraph 0398-0399.
[16]Chemical Science,2020,vol. 11,p. 429 - 434.
[17]Patent: WO2020/33382,2020,A1 .Location in patent: Page/Page column 35; 36.
[18]Patent: CN104341316,2017,B .Location in patent: Paragraph 0293; 0298; 0299.
[19]Journal of Organic Chemistry,2017,vol. 82,p. 982 - 991.
[20]Patent: WO2009/12125,2009,A1 .Location in patent: Page/Page column 55-56; 68-69.
[21]Journal of Medicinal Chemistry,2015,vol. 58,p. 9768 - 9772.
[22]Journal of the Chemical Society. Perkin transactions I,1965,p. 5976 - 5983.
[23]Carbohydrate Research,1991,vol. 218,p. 121 - 127.
[24]Monatshefte fur Chemie,1994,vol. 125,p. 301 - 312.
[25]Tetrahedron Letters,1997,vol. 38,p. 1597 - 1598.
[26]Patent: US2008/96921,2008,A1 .Location in patent: Page/Page column 42; 43; 48; 49; 52; 53.
[27]Tetrahedron Letters,2008,vol. 49,p. 6071 - 6074.
[28]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 5209 - 5212.
[29]Patent: WO2004/48349,2004,A1 .Location in patent: Page 46.
[30]Patent: WO2004/99164,2004,A1 .Location in patent: Page 40-41; 44; 6/22.
[31]Patent: WO2009/12125,2009,A1 .Location in patent: Page/Page column 18.
[32]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 2969 - 2973.
[33]Tetrahedron,2010,vol. 66,p. 5972 - 5981.
[34]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2011,vol. 50,p. 214 - 222.
[35]Patent: WO2011/20615,2011,A1 .Location in patent: Page/Page column 34; 35.
[36]Journal of Heterocyclic Chemistry,2012,vol. 49,p. 621 - 627.
[37]Tetrahedron,2012,vol. 68,p. 6018 - 6031.
[38]European Journal of Medicinal Chemistry,2014,vol. 87,p. 71 - 78.
[39]Chemical Biology and Drug Design,2015,vol. 86,p. 637 - 647.
[40]Journal of Medicinal Chemistry,2017,vol. 60,p. 9960 - 9973.
[41]Patent: WO2018/190643,2018,A1 .Location in patent: Paragraph 587-589.
[42]Patent: EP3401315,2018,A1 .Location in patent: Paragraph 0047; 0048; 0050.
[43]Patent: KR2018/115126,2018,A .Location in patent: Paragraph 0108; 0236; 0240; 0241.
[44]Patent: WO2018/39384,2018,A1 .Location in patent: Paragraph 00348.
[45]Patent: CN110452235,2019,A .Location in patent: Paragraph 0159; 0164-0166.
[46]Patent: WO2020/249064,2020,A1 .Location in patent: Paragraph 000140; 000150; 000151.
[47]ACS Medicinal Chemistry Letters,2021,vol. 12,p. 1413 - 1420.
[48]Chemical Biology and Drug Design,2022,vol. 99,p. 483 - 495.

4
[ 25185-95-9 ]
[ 6575-27-5 ]

Yield	Reaction Conditions	Operation in experiment
94%	With iron oxide; zirconium(IV) chloride; sodium cyanoborohydride; In neat (no solvent); at 75 - 80℃; for 1h;	General procedure: A mixture of benzaldehyde oxime (0.121 g, 1 mmol) and nano Fe3O4 (0.046 g, 0.2 mmol) (nano particle size≈70 nm) was ground in a porcelain mortar. ZrCl4 (0.233 g,1 mmol) was then added and grinding the mixture was continued for a moment at room temperature. The mortar was heated in an oil bath until the temperature of reaction mixture reaches 75-80 C. NaBH3CN (0.314 g, 5 mmol) wasthen added portion wisely and the mixture was ground for15 min at 75-80 C. After completion of the reaction, H2O(5 mL) was added and the mixture was stirred for 5 min. The mixture was extracted with EtOAc (2 × 5 mL) and then dried over anhydrous Na2SO4. Evaporation of the solvent affords the pure liquid benzylamine in 93 % yield (0.1 g, Table 2, entry 1).

References: [1]Journal of the Iranian Chemical Society,2015,vol. 12,p. 873 - 878.
[2]Journal of the Chinese Chemical Society,2019,vol. 66,p. 535 - 542.
[3]Journal of Medicinal Chemistry,1984,vol. 27,p. 1111 - 1118.

5
[ 25185-95-9 ]
[ 2904-62-3 ]

Yield	Reaction Conditions	Operation in experiment
61%	With pyridine; N-chloro-succinimide; In dichloromethane; at 0℃; for 0.5h;	Oxime b (23 gm, 0.122 moles, 1 eq) was dissolved in DCM (250 ml) and to this N-chlorosuccinimide (19.6 gm, 0.1464 moles, 1.2 eq) was added at 00C followed by the addition of pyridine (13.5 gm, 0.1708 moles, 1.4 eq). The reaction mixture was stirred at 00C for 30 minutes and monitored by TLC. The reaction mass was washed with H2O (500 ml) and the DCM layer was separated, dried over Na2SO4, concentrated and purified immediately by fast column (silica gel, 60-120 mesh, 3-5% EA/hexane). Pale yellow solid of N-oxide c was obtained in 61% yield (14 gm) and used immediately for the next reaction. All the concentrations were done below 45 0C and any increase in the temperature resulted in the decomposition of N-oxide.
61%	With pyridine; N-chloro-succinimide; In dichloromethane; at 0℃; for 0.5h;	Oxime b (23 gm, 0.122 moles, 1 eq) was dissolved in DCM (250 ml) and to this N-chlorosuccinimide (19.6 gm, 0.1464 moles, 1.2 eq) was added at 00C followed by the addition of pyridine (13.5 gm, 0.1708 moles, 1.4 eq). The reaction mixture was stirred at 00C for 30 minutes and monitored by TLC. The reaction mass was washed with H2O (500 ml) and the DCM layer was separated, dried over Na2SO4, concentrated and purified immediately by fast column (silica gel, 60-120 mesh, 3-5% EA/hexane). Pale yellow solid of N-oxide c was obtained in 61% yield (14 gm) and used immediately for the next reaction. All the concentrations were done below 45 0C and any increase in the temperature resulted in the decomposition of N-oxide.

References: [1]Synthetic Communications,1990,vol. 20,p. 1373 - 1377.
[2]Patent: WO2010/104929,2010,A1 .Location in patent: Page/Page column 58-59.
[3]Patent: WO2010/104967,2010,A1 .Location in patent: Page/Page column 59.
[4]Organic Letters,2021,vol. 23,p. 5750 - 5754.
[5]Journal of Organic Chemistry,1981,vol. 46,p. 742 - 750.
[6]Journal of Heterocyclic Chemistry,1989,vol. 26,p. 255 - 256.
[7]Synthesis,2003,p. 2763 - 2764.
[8]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3210 - 3217.
[9]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 2670 - 2674.
[10]Tetrahedron,2012,vol. 68,p. 6018 - 6031.
[11]Organic Process Research and Development,2017,vol. 21,p. 771 - 778.

6
[ 25185-95-9 ]
[ 107-08-4 ]
2,6-Dichloro-benzaldehyde O-propyl-oxime [ No CAS ]

References: [1]Monatshefte fur Chemie,1997,vol. 128,p. 659 - 673.

7
[ 42558-54-3 ]
[ 25185-95-9 ]
[ 278597-28-7 ]

References: [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 2971 - 2974.

8
[ 25185-95-9 ]
[ 50-30-6 ]

References: [1]Synthetic Communications,2001,vol. 31,p. 3151 - 3159.

9
[ 25185-95-9 ]
[ 84348-38-9 ]
3-(2,6-dichloro-phenyl)-1-oxa-2,7-diaza-spiro[4.4]non-2-ene-7,8-dicarboxylic acid 7-tert-butyl ester [ No CAS ]

References: [1]Journal of Organic Chemistry,2002,vol. 67,p. 5673 - 5677.

10
[ 25185-95-9 ]
[ 163190-46-3 ]
tert-butyl (5R,8S)-3-(2,6-dichlorophenyl)-1-oxa-2,7-diazaspiro[4.4]non-2-ene-7-N-Boc-8-carboxylate [ No CAS ]
[ 453524-63-5 ]

References: [1]Journal of Organic Chemistry,2002,vol. 67,p. 5673 - 5677.

11
[ 25185-95-9 ]
ethyl N-Boc-4-methylene-L-prolinate [ No CAS ]
3-(2,6-dichloro-phenyl)-1-oxa-2,7-diaza-spiro[4.4]non-2-ene-7,8-dicarboxylic acid 7-tert-butyl ester 8-ethyl ester [ No CAS ]

References: [1]Journal of Organic Chemistry,2002,vol. 67,p. 5673 - 5677.

12
[ 25185-95-9 ]
(4-propionyl)phenyl N-Boc-4-methylene-L-prolinate [ No CAS ]
(4-propionyl)phenyl (5R,8S)-3-(2,6-dichlorophenyl)-1-oxa-2,7-diazaspiro[4.4]non-2-ene-7-N-Boc-8-carboxylate [ No CAS ]
(4-propionyl)phenyl (5S,8S)-3-(2,6-dichlorophenyl)-1-oxa-2,7-diazaspiro[4.4]non-2-ene-7-N-Boc-8-carboxylate [ No CAS ]

References: [1]Journal of Organic Chemistry,2002,vol. 67,p. 5673 - 5677.

13
[ 25185-95-9 ]
[ 83-38-5 ]

Yield	Reaction Conditions	Operation in experiment
83%	With citric acid; In water monomer; for 0.166667h;Microwave irradiation; Green chemistry;	General procedure: A mixture of 0.2 mmol phenylhydrazone,semicarbazones or oximes and citric acid(0.2 mmol) were mixed together in water (10 mL)was introduced in a 50 mL Erlenmeyer ask and wasplaced in a commercial microwave oven operatingat a power output of 300 W and irradiated for theappropriate time in 30 seconds intervals each.(Table 3). The reaction was monitored by TLC.The product extracted with Chloroform, dried overanhydrous Na2SO4, flter and was chromatographed on silica gel (eluted by ethyl acetate: hexane 2:8)to afford the corresponding products in good toexcellent yields (Table 3). All the products werecharacterized by their physical constants, IR, NMRspectra and comparison with authentic samples.The phenylhydrazones, semicarbazones and oximeswere prepared by standard procedures32.
	With oxygen; benzaldehyde; In toluene; for 2h;Catalytic behavior;	General procedure: In this procedure, a suspension of the heterogeneous catalyst(0.07 g), solvent (5 cm3of toluene), oxime (2 mmol) and benzalde-hyde (6 mol) were mixed in a three necked round bottom flaskwhich was fitted with a equipped water condenser with a balloonfilled of O2. The liquid phase oxidation reactions were carried outat desired temperature with vigorous stirring. After completing thereaction, the catalyst has been separated through filtering and theproducts and the amounts of them have been quantified by GC-MSand GC. Finally, a suitable reaction condition has been optimized.
	With oxygen; benzaldehyde; In toluene; for 2.16667h;Reflux;	General procedure: In this procedure, a suspension of the heterogeneous catalyst(0.15 g), solvent (5 cm3of toluene), oxime (2 mmol) and benzalde-hyde (10 mol) were mixed in a three necked round bottom flaskwhich was fitted with a equipped water condenser with a balloonfilled of O2. The liquid phase oxidation reactions were carried outat desired temperature with vigorous stirring. After completing thereaction, the catalyst has been separated through filtering and theproducts and the amounts of them have been quantified by GC-MSand GC. Finally, a suitable reaction condition has been optimized

	With oxygen; benzaldehyde; In phenyl cyanide; toluene; at 60℃; for 1.91667h;Green chemistry;	General procedure: The heterogeneous aerobic oxidation of oximes were done in 3-necked round-bottom flask fitted with condenser and O2 balloonusing Mn(II)-MetMMNPs. In typical reaction catalyst (140 mg),solvent (5 mL), oxime (2 mmol) and benzaldehyde (5 mmol) weremixed under O2 bubbling and stirred at desired temperature. Atthe end of the reaction, the magnetic catalyst has been separatedand products have been quantified by GC and GC-Mass throughbeing compared with authentic samples. Furthermore, the effectivevarious parameters in catalytic oxidation reaction were examinedin order to achieve highest conversion and selectivity.
	With oxygen; benzaldehyde; In toluene; at 50℃; for 1.66667h;Catalytic behavior;	General procedure: The dendritic catalyst (0.07g), toluene (TOL, 5mL), aldoxime/ketoxime (2mmol), and Bz (5mmol) were placed in a three-necked flask with magnetic stirring. The vessel was fitted with an equipped water condenser with a balloon filled with O2 at a specific time & temperature (Table 3). After completion of the reaction, the dendritic catalyst has been isolated by magnet stick and the AH/KO and the amounts of them have been calculated by GC & GC-MS analysis. Eventually, a favorable catalytic oxygenation condition has been assessed.

References: [1]Synthetic Communications,2002,vol. 32,p. 2195 - 2202.
[2]Journal of the Chinese Chemical Society,2005,vol. 52,p. 1005 - 1009.
[3]Journal of the Chinese Chemical Society,2009,vol. 56,p. 416 - 418.
[4]Oriental Journal of Chemistry,2012,vol. 28,p. 857 - 866,10.
[5]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2007,vol. 46,p. 1208 - 1210.
[6]Synthetic Communications,2003,vol. 33,p. 3455 - 3459.
[7]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2010,vol. 49,p. 1140 - 1143.
[8]Oriental Journal of Chemistry,2017,vol. 33,p. 2030 - 2035.
[9]New Journal of Chemistry,2004,vol. 28,p. 1423 - 1425.
[10]Heterocyclic Communications,2006,vol. 12,p. 407 - 410.
[11]Synthetic Communications,2007,vol. 37,p. 4035 - 4042.
[12]Journal of Molecular Catalysis A: Chemical,2014,vol. 382,p. 41 - 54.
[13]Applied Catalysis A: General,2013,vol. 466,p. 282 - 292.
[14]Polyhedron,2019,vol. 157,p. 90 - 106.
[15]Journal of Alloys and Compounds,2022,vol. 908.

14
[ 25185-95-9 ]
[ 2008-58-4 ]

References: [1]Catalysis science and technology,2015,vol. 5,p. 3754 - 3761.
[2]Organometallics,2012,vol. 31,p. 6482 - 6490.
[3]Chemical Communications,2003,p. 1936 - 1937.
[4]Bulletin de la Societe Chimique de France,1917,vol. <4> 21,p. 222.

15
[ 67-56-1 ]
[ 25185-95-9 ]
[ 54268-07-4 ]