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Chemical Structure| 6579-27-7 Chemical Structure| 6579-27-7

Structure of 6579-27-7

Chemical Structure| 6579-27-7

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Product Details of [ 6579-27-7 ]

CAS No. :6579-27-7
Formula : C7H4Cl3NO
M.W : 224.47
SMILES Code : Cl/C(C1=C(Cl)C=CC=C1Cl)=N\O
MDL No. :MFCD00221426

Safety of [ 6579-27-7 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301-H311-H314-H331
Precautionary Statements:P260-P264-P280-P301+P330+P331+P310-P303+P361+P353+P310+P363-P304+P340+P310-P305+P351+P338+P310-P405-P501
Class:6.1(8)
UN#:2928
Packing Group:

Application In Synthesis of [ 6579-27-7 ]

* 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 [ 6579-27-7 ]

[ 6579-27-7 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 25185-95-9 ]
  • [ 6579-27-7 ]
YieldReaction ConditionsOperation 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.

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  • 2
  • [ 3513-81-3 ]
  • [ 6579-27-7 ]
  • [3-(2,6-dichlorophenyl)-5-hydroxymethyl-4,5-dihydroisoxazol-5-yl]methanol [ No CAS ]
  • 3
  • [ 25185-95-9 ]
  • [ 6579-27-7 ]
YieldReaction ConditionsOperation in experiment
With N-chloro-succinimide; In DMF (N,N-dimethyl-formamide); at 40 - 50℃; for 0.5h; 7.1. 1 Synthesis of 5-Dichloromethyl-3- [4- [3'- (2', 6'- dichlorophenyl)-5'-isoxazolyl] phenyl]-1, 2,4-oxadiazole (See Figure 1); Synthesis of 2, 6-Dichloro-N-hydroxybenzenecarboximidoyl Chloride; The general procedure of R. K. Howe, et al, J. Org. Chem., 1980,45, 3916- 3918 was followed. 2,6-Dichlorobenzaldoxime (25.1 gm, 0.132 mol) was dissolved in dimethylformamide (150 mL). ThenN-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 reduced pressure 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).
  • 4
  • [ 6579-27-7 ]
  • [ 137638-05-2 ]
  • C15H13Cl2NO3 [ No CAS ]
  • 5
  • [ 615-06-5 ]
  • [ 6579-27-7 ]
  • C15H9Cl2NO4 [ No CAS ]
  • 6
  • [ 6579-27-7 ]
  • [ 32249-35-7 ]
  • [ 946426-88-6 ]
YieldReaction ConditionsOperation in experiment
87% To a 50 mL round bottom flask containing <strong>[32249-35-7]methyl 3-cyclopropyl-3-oxopropanoate</strong> (1.3 g, 8.9 mmol) was added triethylamine (2.5 mL, 17.8 mmol). The resulting clear solution was stirred at room temperature for 15 minutes and was cooled in an ice water bath. To the stirring solution was added a solution of 2,6-dichloro-N-hydroxybenzimidoyl chloride (2.0 g, 8.9 mmol) in EtOH (4 mL) over the space of 10 minutes giving a white suspension. After addition, the resulting suspension was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and the residue was purified by flash chromatography on S1O2 (0-10% EtOAc/hexanes, Isco 80 g column) to give methyl 5- cyclopropyl-3-(2,6-dichlorophenyl)isoxazole-4-carboxylate (2.4 g, 7.7 mmol, 87% yield) as a white solid. NMR (500 MHz, CDCh) δ 7.45-7.39 (m, 2H), 7.39-7.33 (m, 1H), 3.71 (s, 3H), 2.93 (tt, J=8.5, 5.2 Hz, 1H), 1.47-1.40 (m, 2H), 1.34-1.27 (m, 2H).
87% To a 50 mL round bottom flask containing <strong>[32249-35-7]methyl 3-cyclopropyl-3-oxopropanoate</strong> (1.3 g, 8.9 mmol) was added triethylamine (2.5 mL, 17.8 mmol). The resulting clear solution was stirred at room temperature for 15 minutes and was cooled in an ice water bath. To the stirring solution was added a solution of 2,6-dichloro-N-hydroxybenzimidoyl chloride (2.0 g, 8.9 mmol) in EtOH (4 mL) over the space of 10 minutes giving a whitesuspension. After stirring at room temperature overnight, the reaction mixture was concentrated in vacuo and the residue was purified by flash chromatography on 5i02 (0- 10% EtOAc/hexanes, Isco 80 g column) to give methyl 5-cyclopropyl-3-(2,6- dichlorophenyl)isoxazole-4-carboxylate (2.4 g, 7.7 mmol, 87% yield) as a white solid. ‘H NMR (500 MI-Tz, CDC13) ö 7.45-7.39 (m, 2H), 7.39-7.33 (m, 1H), 3.71 (s, 3H), 2.93 (if,J=8.5, 5.2 Hz, 1H), 1.47-1.40 (m, 2H), 1.34-1.27 (m, 2H).
87% With triethylamine; In ethanol; at 20℃;Cooling with ice; To a 50 mL round bottom flask containing <strong>[32249-35-7]methyl 3-cyclopropyl-3-oxopropanoate</strong> (1.3 g, 8.9 mmol) was added triethylamine (2.5 mL, 17.8 mmol). The resulting clear solution was stirred at room temperature for 15 minutes and was cooled in an ice water bath. To the stirring solution was added a solution of 2,6-dichloro-N-hydroxybenzimidoyl chloride (2.0 g, 8.9 mmol, synthesis described in General Method A) in EtOH (4 mL) over the space of 10 minutes giving a white suspension. After addition, the resulting suspension was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and the residue was purified by flash chromatography on SiO2 (0-10% EtOAc/hexanes, Isco 80 g column) to give methyl 5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazole-4-carboxylate (2.4 g, 7.7 mmol, 87% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ 7.45-7.39 (m, 2H), 7.39-7.33 (m, 1H), 3.71 (s, 3H), 2.93 (tt, J=8.5, 5.2 Hz, 1H), 1.47-1.40 (m, 2H), 1.34-1.27 (m, 2H).
84% Triethylamine (8.2g) was added to <strong>[32249-35-7]methyl 3-cyclopropyl-3-oxopropionate</strong> (82mmol), Stir for 30 minutes. Then cool to 10C, Then add a solution of III-1 (18.3g, 82mmol) in absolute ethanol (80mL) dropwise (internal temperature does not exceed 30C), The reaction was overnight at room temperature. Add ethyl acetate (100mL) to dilute the reaction solution, wash with water, The aqueous phase was extracted with ethyl acetate (100 mL each time, 3 times in total). Mix the organic phase, Wash with saturated brine and concentrate. Add 100mL ether to the concentrate and stir, The solvent was removed under vacuum to obtain the solid product IV-1 (21.6 g, yield 84%).
65% 3-Cyclopropyl-3-oxo-propionic acid methyl ester (31.7g, 0.223mol) was dissolved by adding triethylamine (45.1g, 62mL, 0.446mol),Stir at room temperature. After 30 minutes, cool down to 10 C.Slowly add 2,6-dichloro-benzaldehyde-chloro-oxime (50.0g, 0.223mol, dissolved in 300mL ethanol), the temperature during the dropwise addition does not exceed 24 C,After dripping, stir overnight at room temperature, monitor the reaction by thin layer chromatography (TLC), and add 200 mL of water after the reaction.Extracted with 500 mL of ethyl acetate (EA), extracted the aqueous layer three times with 200 mL of ethyl acetate, combined the organic layers, washed the organic layer with 200 mL of saturated brine, and dried over anhydrous Na2SO4.Concentrated in vacuo to 10% solution, a large amount of solids precipitated,The crude product was obtained by suction filtration, followed by grinding with 100 ml of hexane, suction filtration, and drying to obtain 45.0 g of a white solid with a yield of 65%.
54% Triethylamine (10.91 g, 0.11 mol, 2.0 eq) was added to a mixture of <strong>[32249-35-7]methyl 3-cyclopropyl-3-oxopropionate</strong> (7.66 g, 0.054 mol, 1.0 eq) and stirred at room temperature for 30 min, And then cooled to 10 C.The intermediate 1-9 (12.10 g,0.054 mol, 1.0 eq) was dissolved in 24.2 mL of ethanol and slowly added to the above reaction solution, and the internal temperature did not exceed 24 C. In addition,Stir overnight at room temperature.After completion of the reaction, the reaction solution was diluted with 45 ml of ether, washed with 15 ml of water, separated, and the aqueous layer was extracted once with ethyl acetate.And the organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to 10% of the total to form a precipitate which was washed with etherMashing beating, filtering, filter cake vacuum dry,To give intermediate 1-10, 8.48 g of a white solid,the yield was 54%.
54% Triethylamine (10.91 g, 0.11 mol, 2.0 eq) was added to <strong>[32249-35-7]methyl 3-cyclopropyl-3-oxopropanoate</strong>(7.66 g, 0.054 mol, 1.0 eq) mixture was stirred at room temperature for 30 min and then cooled to 10 C.Intermediate 1-9 (12.10 g, 0.054 mol, 1.0 eq) was dissolved in 24.2 mL of ethanol.The reaction solution was slowly added thereto, and the internal temperature did not exceed 24 C. Further, the reaction was stirred at room temperature overnight. After the reaction, the reaction solution was diluted with 45 ml of EA, washed with 15 ml of water, and the mixture was evaporated.The organic layers were combined, washed with brine and dried over anhydrous sodium sulfateFilter and concentrate the filtrate to 10% of the total amount.A precipitate formed, which was beaten with ether and filtered, and the cake was vacuum dried.Intermediate 1-10 was obtained as a white solid, 8.48 g, yield 54%.

 

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