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CAS No. : | 38945-21-0 | MDL No. : | MFCD00012957 |
Formula : | C3H8ClNO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | XIQUJVRFXPBMHS-UHFFFAOYSA-N |
M.W : | 109.55 | Pubchem ID : | 3084724 |
Synonyms : |
|
Num. heavy atoms : | 6 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.33 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 26.82 |
TPSA : | 35.25 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.41 cm/s |
Log Po/w (iLOGP) : | 0.0 |
Log Po/w (XLOGP3) : | 0.78 |
Log Po/w (WLOGP) : | 0.86 |
Log Po/w (MLOGP) : | 0.49 |
Log Po/w (SILICOS-IT) : | -0.47 |
Consensus Log Po/w : | 0.33 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -0.88 |
Solubility : | 14.5 mg/ml ; 0.132 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.1 |
Solubility : | 8.69 mg/ml ; 0.0793 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | 0.02 |
Solubility : | 116.0 mg/ml ; 1.06 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 2.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.86 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: With methylhydrazine In dichloromethane at 0 - 20℃; for 2 h; Stage #2: With hydrogenchloride In 1,4-dioxane at 0℃; |
After 500 mg of hydroxyphthalimide (Aldrich) was dissolved in 5 ml of dimethylformamide under argon flow, 0.3 ml of allyl iodide (Aldrich) was added, and 0.5 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene (Aldrich) was slowly added. After the mixture was stirred at room temperature for 1 hour and 20 minutes, the reaction was stopped by adding a 2 N hydrochloric acid solution. The reaction liquid was diluted by adding 20 ml of ethyl acetate, followed by drying over magnesium sulfate and then filtering. The filtrate was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography using a mixture eluent of ethyl acetate/hexane (1:5) and then dried to obtain 498 mg of a compound (yield: 80percent). The compound was dissolved in 5 ml of dichloromethane, and 0.11 ml of methyl hydrazine (TCI) was slowly added at 0° C. After the reaction liquid was stirred at room temperature for 2 hours, the temperature was again lowered to 0° C. The generated solid was then filtered out, and 1 ml of a 4 M-hydrochloric acid dioxane solution (Aldrich) was added to the residual filtrate, followed by filtration and drying, to obtain 236 mg of a solid (yield: 88percent). 16 mg of the obtained solid and 66 mg of SAC-0906 obtained as obtained above were dissolved in 1 ml of pyridine (Aldrich) under argon flow, followed by stirring at 80° C. for 4 hours. After the temperature was lowered to room temperature, the reaction liquid was acidified by adding a 2 N hydrochloric acid solution, followed by extraction with 20 ml of diethyl ether, drying over magnesium sulfate, and filtering. The filtrate was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography using a mixed eluent of ethyl acetate/hexane (1:5) to obtain the target compound SAC-1011 (63 mg, yield: 86percent). 1H-NMR (300 MHz, CDCl3) δ6.02-5.89 (m, 1H), 5.86-5.76 (m, 2H), 5.34-5.32 (m, 1H), 5.28-5.19 (m, 2H), 5.15-5.11 (m, 2H), 4.52-4.50 (m, 2H), 4.24-4.12 (m, 3H), 3.58-3.48 (m, 1H), 2.42-0.60 (m, 35H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With N,N,N,N,N,N-hexamethylphosphoric triamide; hydroxylamine hydrochloride; N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide In N,N-dimethyl-formamide at 30 - 40℃; for 1 h; Inert atmosphere; Large scale | Under nitrogen gas environment, the reactor was put into acetate 810kg (molecular weight 74,11.0kmol), hydroxylamine hydrochloride 500kg (molecular weight 69.5,7.2kmol), 2kgDMF, stirred for 0.5 hour, to maintain 20-30 , dropping concentration of 30 mass percent sodium hydroxide solution 1000kg (7.5kmol), after the completion of dropwise addition, the reaction was kept 1 hour;After completion of the reaction, the reaction mixture was added to 2kg benzyl triethyl ammonium chloride and 970 kg of 1,3-dichloropropene (molecular weight 111,8.7kmol), was added dropwise a concentration of 30 mass percent sodium hydroxide solution 1000kg (7.5kmol ), and the reaction temperature was controlled at 30-40 deg.] C, the reaction was stirred for 1 hour;To the reaction solution was added at a concentration of 30percent by mass of hydrochloric acid 1000kg (8.2kmol), the reaction was warmed to 50-60 , incubated for 3 hours, the reaction was cooled to room temperature, added to a concentration of 30 mass percent sodium hydroxide solution and to pH7 -, toluene was added to 500kg, and extracted three times, to the water layer, the toluene solution of hydroxylamine O- allyl chloride to give the product desolventizing 720kg hydroxylamine O- allyl chloride (molecular weight 107.5,6.7kmol), yield 93.0percent, content ≥99percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With hydrogenchloride In water at 110℃; for 2 h; | Ethyl O-allyl acetohydroxamate (154.85 g, 0.85mol, 1eq) was added into a solution of 3 mol/L hydrochloric acid (425mL, 1.275mol, 1.5eq) for reflux reaction, at same time magnetic stirring, and heated at 110 ° C and carry on reaction for 2h, the reaction solution was concentrated with a water pump and precipitated as a white solid, the white solid was pulverized with methanol and dried and obtained 783.8 g of white crystals, melting point is 170.3 ° C, the titration purity is 98.8percent, and the yield is 90percent |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With potassium carbonate; In methanol; water; at 0 - 20℃; for 16h; | General procedure: Compounds 21 and 32 were synthesized by treatment of the commercially available aminoxyhydrochloride with p-toluenesulfonyl chloride (1 equiv) in the presence of potassiumcarbonate (3 equiv) in a MeOH/H2O solution (3:2) at 0 C and the solution was stirred at rt.(Scheme 1, eq 1) After 16 h, methanol was removed and the remained aqueous solution wasacidified to neutral pH and the products were extracted three times with ethyl acetate. Thecombined organic layers were washed with brine, dried over MgSO4, filtered andconcentrated in vacuo. The crude products were purified by flash chromatography on silicagel (petroleum ether/ethyl acetate) to obtain the N-tosyl alkoxyamines 2 and 3. (Scheme 1, eq1). |
101.3 g | To a solution of N-hydroxyphthalimide S-2 (100 g, 0.613 mol) in DMSO (1.1 L) wereadded K2CO3 (85.6 g, 0.619 mol) and allyl chloride (50.0 mL, 0.613 mol). After stirringfor 48 h at room temperature, the reaction mixture was poured into ice water toprecipitate the solid, which were collected by filtration and washed with hexane toafford phthalimide S-3 (108 g) as a white solid. This material was employed in the next experiment without further purification.To a solution of crude S-3 (108 g, 0.532 mol) in EtOH (1.8 L) was added H2NNH2·H2O(25.9 mL, 0.533 mol). After stirring for 16 h at 80 C, additional H2NNH2·H2O (2.6 mL,53 mmol) was added to the reaction mixture. After stirring for 5 h at 80 C, the mixturewas cooled to room temperature. Precipitates were filtered, and to the resulting filtratewas added conc. HCl (77 mL). The mixture was concentrated in vacuo to afford alkoxyamine hydrochloride S-4 as a white solid, contaminated with a trace amount of impurity (assessed by 1H NMR). This material was employed in the next experimentwithout further purification.To a suspension of crude S-4 in THF (1.3 L) was added a solution of K2CO3 (111 g,0.800 mol) in H2O (0.5 L) at 0 C. After stirring for 1 h at this temperature, TsCl (91.5 g,0.480 mol) was added to the mixture, which was stirred for 15 h at room temperature.The products were extracted with EtOAc (x3). The combined organic extracts werewashed with brine, dried (Na2SO4), and concentrated in vacuo. Recrystallization withEtOAc and hexane gave alkoxyamide 26 as colorless needles [1st crop: 88.2 g, 63%,2nd crop: 13.1 g, 9%; total yield = 72% (3 steps)].Rf 0.46 (hexane/EtOAc = 2/1); mp 93-94 C (CHCl3/hexane, colorless needle); 1HNMR (600 MHz, CDCl3) delta 2.45 (s, 3H), 4.46 (d, 2H, J = 6.6 Hz), 5.26 (d, 1H, J = 10.2Hz), 5.30 (d, 1H, J = 16.8 Hz), 5.89 (ddt, 1H, J = 16.8, 10.2, 6.6 Hz), 6.97 (brs, 1H),7.35 (d, 2H, J = 7.8 Hz), 7.82 (d, 2H, J = 7.8 Hz); 13C NMR (150 Hz, CDCl3) delta 21.7,78.1, 120.1, 128.6, 129.7, 132.0, 133.6, 144.9; IR (ATR) 3217, 1597, 1404, 1328, 1303,1163, 1088, 1034, 999, 938, 889, 812 cm-1; Anal. Calcd for C10H13NO3: C, 52.85; H,5.77; N, 6.16; S, 14.11; Found: C, 52.71; H, 5.69; N, 6.16; S, 13.85. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With sodium acetate; In methanol; water; at 20℃; | NaOAc (3 G, 10. 17 mmol) followed by O-allyl-Hydroxylamine hydrochloride (4. 5 G, 41. 4 mmol) were added to a solution of estrone (1 g, 3. 70 mmol) in A MIXTURE OF MEOH/H2O (5: 1,180 mL). The resulting solution was stirred at room temperature overnight. The solvent was then removed under reduced pressure and water added (200 mL). The organics were extracted with EtOAc (200 mL + 100 mL), washed with water (2x100 mL) then brine (2x100 mL), dried (NA2SO4), FILTERED AND CONCENTRATED under reduced pressure to give A white crude (1. 37 g). This was recrystallized from MeOH/H2O and gave the product as white crystals (1. 13 G, 94%) : TLC (chloroform/EtOAc, 8 : 2) RF 0. 66 CF. RF 0.56; No. H (CDCL3, 400 MHZ) 0. 94 (3H, s, C-18-H3), 1.35-2.60 (13H, m), 2.80-2.87 (2H, m, C-6-H2), 4. 55 (2H, ddd, JAB = 5.5 Hz, JC-2'-H,C-1'-H = 2.7 Hz and JC-3'-H,C-1'-H = 1.4 Hz, C-1'-H2), 4.74 (1H, s, echanged with D2O, OH), 5. 19 (1H, ddd, Jcis = 10.3 Hz, JC-1'-H,C-3'-H = 1. 4 Hz, C-3 -HA), 5. 28 (1H, d, Jtrans = 17.2 Hz, JC-1'-H,C-3'-H = 1.6 Hz, C-3'-Hb), 5.59-6.01 (1H, m, C-2 -H), 6. 56 (1H, d, Jc-2-H, C-4-H = 2.7 Hz, C-4-H), 6.63 (1H, dd, JC-1-H, C-2-H = 8.2 Hz and JC-4-H, C-2-H = 2. 7 HO, C-2-H) and 7. 15 (1H, d, JC-2-H, C-1-H = 8. 2 Hz, C-1-HJ ; MS M/Z (FAB. +) 326. 1 [100, (M+H) +], 268. 1 [30, OCH2CH=CH2+] ; Acc MS m/z (FAB+) 326. 21157, C21H28NO2 requires 326.21200. Found: C, 76.40 ; H, 8.24 ; N, 4. 36. C21H27NO2 requires: C, 76.23 ; H, 8.50 ; N, 4.17. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sodium acetate; In ethanol; at 80℃; for 2h; | Compound 2: To a vial charged with 1 (50 mg, 0.15 mmol) was added sodium acetate trihydrate (52 mg, 0.41 mmol) and o-allylhydroxylamine hydrochloride (26 mg, 0.24 mmol) followed by ethanol (0.5 mL). The vial was sealed an the reaction heated in an 80 C. oil-bath for 2 hours. The reaction was cooled to room temperature, diluted with chloroform (10 mL) and extraced with H2O (3×10 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo to give 2 (56 mg, 95% yield) as a white solid. Rt=1.91 min using Phenomenex 30×4.6 5u column with flow rate of 5 mL/min over 2 min gradient. 0 to 100% B. Solvent A=10/90/0.1% MeOH/H2O/TFA. Solvent B=90/10/0.1%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.0% | With sodium acetate; potassium carbonate; In ethanol; at 80℃; for 1.5h; | In a 3 liter-three-necked flask, 166.0 g (1036 mM) of 1-benzosuberone, 125.0 g (1141 mM) of <strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong>, 93.5 g (1140 mM) of sodium acetate, 158.0 g (1143 mM) of potassium carbonate and 1500 ml of ethanol were placed and heat-stirred for 1.5 hour at 80 C. The reaction product was cooled to room temperature and the solvent was removed under reduced pressure to obtain a residue. To the residue, 1500 ml of water was added, followed by extraction three times each with 500 ml of ethyl acetate. The organic layer was dried with anhydrous magnesium sulfate, followed by removal of the solvent under reduced pressure to obtain a pale brown liquid. The liquid was subjected to distillation under reduced pressure to obtain 221.8 g (Yield: 99.0 %) of 1-benzosuberone=oxime=O-allyl=ether (boiling point = 75 = 83 C (4.0 Pa)). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84.6% | With sodium acetate; In methanol; water; at 20℃; for 12h; | 13, 69 G (91,28 mmol) FORMYLPHENYLBORONSaeURE, 10, 0 g O-Allylhydroxylamin-Hydro- chlorid (91,28 mmol) und 9,36 g (114, 10 mmol) Natriumacetat werden 12 h bei Raumtem- peratur in einem Gemisch aus 100 ml Methanol und 40 ml Wasser geruehrt. Zur Aufarbeitung wird unter vermindertem Druck eingeengt, der Rueckstand in 150 ml Wasser verruehrt, ueber einer Glasfritte abgesaugt, mit wenig Wasser gewaschen und auf einem Tonteller getrocknet. Man erhaelt 16,5 g (84,6 % der Theorie) an 4-Allyloxyiminomethyl-phenyl-boronsaeure. H-NMR (DMSO-d6) : A = 8,27 ppm (s, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With triethylamine; In ethanol; at 20℃; for 4h; | Compound 197: 1-[2-(6,7-Dimethoxy-quinolin-4-yloxy)-4,5-dimethyl-phenyl]-ethanone o-allyl-oxime; 1-[2-(6,7-Dimethoxy-quinolin-4-yloxy)-4,5-dimethylphenyl]-1-ethanone (compound 38) (30 mg) was dissolved in ethanol (1 ml) to prepare a solution. Allyloxyamine hydrochloride (29 mg) and triethylamine (27 mg) were added to the solution, and the mixture was stirred at room temperature for 4 hr. The solvent was removed by distillation under the reduced pressure, and the residue was purified by column chromatography using hexane-acetone to give the title compound (32 mg, yield 88%). 1H-NMR (CDCl3, 400 MHz): delta 2.10 (s, 3H), 2.27 (s, 3H), 2.31 (s, 3H), 4.04 (s, 3H), 4.05 (s, 3H), 4.50 (ddd, J = 1.4, 1.4, 5.6 Hz, 2H), 5.04 - 5.16 (m, 2H), 5.79 - 5.91 (m, 1H), 6.38 (d, J = 5.1 Hz, 1H), 6.93 (s, 1H), 7.31 (s, 1H), 7.41 (s, 1H), 7.54 (s, 1H), 8.45 (d, J = 5.1 Hz, 1H) Mass spectrometric value (ESI-MS, m/z): 407 (M+1)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With sodium carbonate; In water; benzene; at 0 - 20℃; for 12h; | The N-alcoxyamines 2a-c were purchased from Aldrich and Fluka Companies, and used without further purification. The N-alcoxyamine 2d was prepared following the procedure described in Brown, D. S.; Gallagher, P. T.; Lightfoot, A. P.; Moody, C. J.; Slawin, A. M. Z.; Swann, E. Tetrahedron 1995, 51, 11473-11488. To a vigorously stirred solution of N-alcoxyamine hydrochloride 2a-d (17.87 mmol) and sodium carbonate (32.50 mmol) in a mixture of benzene (23 ml) and H2O (23 ml) with ice-water bath cooling, was added 4-methoxyphenylacetyl chloride (1). The mixture was stirred at room temperature for 12 h under an argon atmosphere and the progress of the reaction was monitored by TLC (hexane-AcOEt, 1:2). Then, AcOEt (50 ml) was added and the organic layer separated. This process was repeated three times. The combined extracts were washed with brine (2 x 50 ml), dried over Na2SO4, filtered and concentrated under reduced pressure to give the corresponding N-alcoxyamide 3a-d, which was used in the next reaction without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With sodium acetate; In ethanol; at 20℃; for 15h; | Example 7C Preparation of N-[2-(1-allyloxyiminoethyl)-5-trifluoromethylphenyl]trifluoromethanesulfonamide (Compound 241) A solution of N-(2-acetyl-5-trifluoromethylphenyl)trifluoromethanesulfonamide 35 (168 mg, 0.50 mmol), <strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (60mg, 0.53 mmol) and anhydrous NaOAc (43 mg, 0.53 mmol) in EtOH (3 mL) was stirred for 15 hours at RT. The reaction mixture was concentrated under vacuum, and the residue purified by radial thin layer chromatography (eluting with CH2Cl2/PE, 1:99) to afford N-[2-(1-allyloxyiminoethyl)-5-trifluoromethylphenyl]trifluoromethanesulfonamide 241 (155 mg, 80%), as a colorless oil. 1H n.m.r. (400 MHz, CDCl3) 5 11.82, br s, 1H; 7.98, s, 1H; 7.65, d, J=8.2Hz, 1H; 7.49, d, J=8.2Hz, 1H; 6.02, m, 1H; 5.44, d, 3J=1H; 5.37, d, 3J=10.4 Hz, 1H; 4.72, d, J=6.0 Hz, 2H; 2.38, s, 3H. HRMS (M+) 390.0465. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; 1,1'-carbonyldiimidazole; In tetrahydrofuran; | EXAMPLE Y-3 2-Amino-N-allyloxy-4,5-difluoro-benzamide Carbonyldiimidazole (3.37 g, 20 mmol) was added to a suspension of 4,5-difluoroanthranilic acid (3.0 g, 17 mmol) in 80 mL of THF, and the mixture was heated to reflux for 2 hours. The solution was cooled and O-allylhydroxylamine hydrochloride (1.89 g, 17 mmol) and triethylamine (2.8 mL, 20 mmol) were added, and the mixture was heated to reflux for 17 hours. The reaction mixture was concentrated and washed with 1N HCl, saturated NaHCO3, and brine and dried over magnesium sulfate. The solution was concentrated and purified by column chromatography (silica gel, CHCl3/MeOH, 98:2) to give 2.08 g of the title compound as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | In N,N-dimethyl-formamide; at 50℃; for 5h; | a solution of trans 4-formyl-cinnamic acid A (Y?CH?CH, R1, ?H, R3?H, 0.346 g, 1.96 mmol.) and B <strong>[38945-21-0]O-Allylhydroxylamine hydrochloride</strong> (0.258 g, 2.37 mmol.) dissolved in 2 mL of DMF was warmed at 50 C. and stirred for 5 h. Then the solution was diluted with AcOEt and washed with water. Organic layer was dried on Na2SO4 and then concentrated under reduced pressure to give 0.421 g of the intermediate C (2E)-3-(4-[(benzyloxy)imino]methyl}phenyl)acrylic acid (93% yield). |
93% | In N,N-dimethyl-formamide; at 50℃; for 5h; | a solution of trans 4-formyl-cinnamic acid A (Y = CH=CH, Ri = H, R3 = H, 0.346 g, 1.96 mmol.) and B <strong>[38945-21-0]O-Allylhydroxylamine hydrochloride</strong> (0.258 g, 2.37 mmol.) dissolved in 2 ml_ of DMF was warmed at 50 0C and stirred for 5 h. Then the solution was diluted with AcOEt and washed with water. Organic layer was dried on Na2SO4 and then concentrated under reduced pressure to give 0.421 g of the intermediate C (2£)-3-(4-[(benzyloxy)imino]methyl}phenyl)acrylic acid (93 % yield).MS (ESI) m/z: [M-1 ]" = 230.3 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With sodium hydrogencarbonate; In tetrahydrofuran; methanol; at 20℃; for 4h; | (9aS)-8-Acetyl-N-[4-(2-butynyloxy)-2,3,6-trimethylbenzyl]-1,7-dihydroxy-3-methoxy-9a-methyl-9-oxo-9,9a-dihydrodibenzo[b,d]furan-4-carboxamide produced in Example (102b) (210 mg, 0.38 mmol) was dissolved in tetrahydrofuran:methanol (2:1, 5 mL). <strong>[38945-21-0]O-Allylhydroxylamine hydrochloride</strong> (63 mg, 0.58 mmol) and sodium bicarbonate (49 mg, 0.58 mmol) were added at room temperature, and the mixture was stirred for four hours. The reaction solution was treated in the same manner as in Example 87 to give the title target compound (159 mg, 69%) as a yellow solid. 1H-NMR (CDCl3, 400NMz):delta ppm: 1.63 (3H, s), 1.72 (3H, s), 1.87 (3H, s), 2.17 (3H, s), 2.31 (3H, s), 2.41 (3H, s), 2.56 (3H, s), 3.77 (3H, s), 4.54-4.63 (6H, m), 5.41-5.48 (2H, m), 5.87 (1H, s), 6.00 (1H, m), 6.21 (1H, s), 6.63 (1H, m), 6.68 (1H, s), 11.20 (1H, s), 15.84 (1H, brs) MS (ESI) m/z: 601 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With sodium hydrogencarbonate; In tetrahydrofuran; methanol; at 20℃; for 4h; | (9aS)-8-Acetyl-1,7-dihydroxy-3-methoxy-9a-methyl-N-[(2-methyl-1-naphthyl)methyl]-9-oxo-9,9a-dihydrodibenzo[b,d]furan-4-carboxamide produced in Example 27 (202 mg, 0.40 mmol) was dissolved in tetrahydrofuran:methanol (2:1, 5 mL). <strong>[38945-21-0]O-Allylhydroxylamine hydrochloride</strong> (53 mg, 0.49 mmol) and sodium bicarbonate (41 mg, 0.49 mmol) were added at room temperature, and the mixture was stirred for four hours. The reaction solution was treated in the same manner as in Example 87 to give the title target compound (200 mg, 89%) as a yellow solid. 1H-NMR (CDCl3, 400MHz):delta ppm: 1.70 (3H, s), 2.55 (3H, s), 2.62 (3H, s), 3.59 (3H, s), 4.54 (2H, d, J=6.4Hz), 5.01-5.13 (2H, m), 5.41-5.47 (2H, m), 5.86 (1H, s), 5.99 (1H, m), 6.16 (1H, s), 7.00 (1H, m), 7.33 (1H, d, J=8.3Hz), 7.43 (1H, m), 7.53 (1H, m), 7.72 (1H, d, J=8.3Hz), 7. 81 (1H, d, J=8.3Hz), 8.11 (1H, d, J=8.3Hz), 11.21 (1H, s), 15.84 (1H, brs) MS (ESI) m/z: 555 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sodium hydrogencarbonate; In tetrahydrofuran; methanol; at 20℃; for 4h; | (9aS)-8-Acetyl-N-(4- { [(2,4-dichlorophenyl)sulfonyl] amino } -2,6-dimethylbenzyl)-1,7-dihydroxy-3-methoxy-9a-methyl-9-oxo-9,9a-dihydrodibenzo[b,d]furan-4-carboxamide produced in Example (111b) (0.300 g, 0.436 mmol) was dissolved in tetrahydrofuran (6 mL) and methanol (3 mL). Sodium bicarbonate (0.044 g, 0.524 mmol) and <strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (0.057 g, 0.524 mmol) were added, and the mixture was stirred in a nitrogen atmosphere at room temperature for four hours. After completion of the reaction, dilute hydrochloric acid (10 mL) was added, followed by extraction with ethyl acetate (12 mL). The organic layer was washed with brine and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (elution solvent: methylene chloride/methanol = 50/1) to give the target compound (0.308 g, yield: 95%) as a yellow powder. 1H-NMR (CDCl3, 500MHz):delta ppm: 1.70 (3H, s), 2.33 (6H, s), 2.55 (3H, brs), 3.74 (3H, s), 4.45-4.56 (2H, m), 4.56 (2H, d, J=5.9Hz), 5.44 (1H, d, J=10.7Hz), 5.86 (1H, d, J=17.1Hz), 5.86 (1H, s), 6.00 (1H, m), 6.22 (1H, s), 6.71 (1H, brs), 6.79 (2H, s), 6.91 (1H, brs), 7.33 (1H, dd, J=2.0, 8.6Hz), 7.52 (1H, d, J=2.0Hz), 7.98 (1H, d, J=8.6Hz), 11.29 (1H, s), 15.90 (1H, s). MS (ESI) m/z: 742.1381 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 1: Treat a solution of 3,4-dichlorophenylacetic acid (25 g) with N-t-BOC-sarcosine methyl ester (24.3 g) (prepared from sarcosine methyl ester HCl and di-t-butyldicarbonate) according to a procedure similar to Example 11, Step 2, to give the desired product (36 g).Step 2 : Treat 2-bromoethanol (107 g) in CH2Cl2 (2 L) at 0 C with t-butyldimethylsilyichloride (143 g), NEt3 (130 g) and DMAP (11 g), allow the reaction mixture to warm to 23 C and stir for 18 h. Wash the mixture with H2O (250 mL), 20% HCl (250 mL), 20% NH4OH (250 mL), dry (MgSO4) and concentrate to give 2-(t-butyldimethylsilyloxy)-ethylbromide (197 g).Step 3 : Treat the product of Step 1 (57 g) in DMF (500 mL) at -10 C with NaH (8.6 g, 60% disp. in oil) and stir for 1 h. Add 2-(t-butyldimethylsilyloxy)ethylbromide (51.3 g) and Nal (6.4 g) and stir for 18 h. Add EtOAc (400 mL) and saturated NaCl solution (300 mL). Separate the organic portion, dry (MgSO4), filter and concentrate. Purify the crude oil by silica gel chromatography eluting with EtOAc/hexane mixtures to give product (60.1 g).Step 4 : Treat the product from Step 3 (28 g) with O-allylhydroxylamine HCl (17 g) according to a procedure similar to Example 1, to give the title compound (24.5 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With triethylamine; In methanol; acetonitrile; at 50℃; for 18h; | To a mixture of 4-chloro-2-(3-methoxybenzyl)-5-fluoropyrimidine (0.151 g, 0.558 mmol) and <strong>[38945-21-0]O-allyl hydroxylamine hydrochloride</strong> (0.201 g, 1.83 mmol) in 5:1 MeOH:CH3CN (5 mL) was added triethylamine (0.273 g, 2.70 mmol) and the mixture was heated at 50 C. for 18 h. The reaction was cooled to room temperature and diluted with Et2O (50 mL). The organic solution was washed with water (2×50 mL), dried over MgSO4, filtered, and concentrated. Purification by flash chromatography (SiO2, 17%->50% EtOAc/hexane) afforded O-allyl-N-(5-fluoro-2-(3-methoxybenzyloxy)-pyrimidin-4-yl)hydroxylamine (0.113 g, 66% yield) as a colorless oil: 1H NMR (300 MHz, DMSO-d6) delta 10.94 (broad singlet, 1H), 7.94 (broad singlet, 1H), 7.28 (t, J=8.0 Hz, 1H), 6.95-7.03 (m, 2H), 6.88 (dd, J=2.5, 7.9 Hz, 1H), 5.97 (tdd, J=5.8, 10.6, 17.0 Hz, 1H), 5.32 (dd, J=1.5, 17.4 Hz, 1H), 5.24 (s, 2H), 5.22 (dd, J=1.2, 10.6 Hz, 1H), 4.39 (d, J=6.0 Hz, 2H), 3.74 (s, 3H); MS (ESI) m/z 306 (M+H)+, 304 (M-H)-. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With sodium hydroxide; In dichloromethane; water; at 23℃; for 18h; | Di-tert-butyl dicarbonate (11 g, 50 mmol, 1.1 equiv) and powdered NaOH (3.7 g, 91 mmol, 2.0 equiv) were sequentially added to a stirred biphasic mixture of O-2-propenylhydroxylamine hydrochloride (5.0 g, 46 mmol, 1.0 equiv) in 1:1 CH2Cl2:water (150 mL) at 23 C. The resulting white biphasic mixture was vigorously stirred at 23 C. for 18 h. The reaction mixture was diluted with water (H2O; 100 mL) and extracted with CH2Cl2 (100 mL). The organic layer was dried over Na2SO4, gravity filtered, and concentrated by rotary evaporation to afford a colorless oil (7.3 g, 92%): 1H NMR (300 MHz, CDCl3) delta 7.11 (br s, 1H), 5.96 (m, 1H), 5.31 (m, 2H), 4.34 (dt, J=6, 1 Hz, 2H), 1.48 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Compound 3 was also prepared in the following manner. 4-Amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinic acid (29.6 g, 89.39 mmol) was dissolved in anhydrous DMF (280 mL) under nitrogen. 1,1'-Carbonyldiimidazole (16.16 g, 99.66 mmol, 1.1 equiv) was added. After stirring for 30 min, solid <strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (11.11 g, 101.41 mmol, 1.1 equiv) was added. After 3 h, the reaction mixture was poured into H2O (1400 mL). The resulting precipitate was filtered, washed with H2O and dried to give a white solid (32.1 g, 93%) which was found to be 98% pure by high-performance liquid chromatography (HPLC). 1H NMR and LC-MS data matched that above. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | Example 70 Preparation of Compound 118, N-Allyloxy-2-[(S)-2-benzyl-4-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazin-1-yl]-acetamide Prepared by the method outlined for Example 62 using <strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (with 1 equivalent of triethylamine to neutralize hydrochloride salt) as the amine component. Oil (71%). LC/MS 5.46 min, [M+1]+ 480. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | General procedure: A mixture of 3,4-dichlorophenyl-cyanamide (1.0 equiv) (14) and alkoxylamine HCl salt (2.0 equiv) in absolute ethanol was heated under reflux for 18 h. The solvent was removed under reduced pressure. Saturated aqueous Na2CO3 was added to the residue. The mixture was extracted with ethyl acetate three times. The organic extracts were combined, washed with brine, dried over Na2SO4, filtered, and the solvent was evaporated to dryness under reduced pressure. The residue was suspended in small amount of cold (4 C) CH2Cl2, filtered and washed with fresh CH2Cl2 to give white solid. Compounds 12a-e was used for reactions without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With sodium hydroxide; In 1,4-dioxane; water; at 60℃; for 4h; | A mixture of 2-chloro-N-(4, 6-bis-(n-propylamino)-[1,3,5]triazine (XXXIV) (2.00 g, 8.71 mmol), <strong>[38945-21-0]O-allyl-hydroxylamine hydrochloride</strong> (1.91 g, 17.42 mmol) and NaOH (0.70 g, 17.42 mmol) in 1,4-dioxane (25 mL) and water (5 mL) was heated at 60 C for 4 h. The volatiles were removed under reduced pressure.Saturated NaHC<¼ solution (100 mL) was added to the residue and the mixture was extracted with EtOAc (3 x 25 mL). The combined organic extracts were washed with water (50 mL), brine (50 mL) and dried over Na2SO.j. The solvent was removed under reduced pressure and the crude product was purified by flash column chromatography using gradient elution from ClfcCMtOH (99:1) to CH2Cl2 EtOH (95:5) to yield 0-allyl-N-(4,6-bis-propylamino-[ 1 ,3,5]triazin-2-yl)-hydroxylamine (XLIII, 2.05 g, 88% yield). ESI-MS (m/z) 267 [ +H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | 23.4: tert-Butyl [(S)-2-allyloxycarbamoyl-2-(4-isobutylylpiperazin-1-yl)ethyl]carbamate; 1.4 g (4.4 mmol) of O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluroniumtetrafluoroborate and then 2.3 ml (13.1 mmol) of diisopropylethylamine are added to a solution of 1.5 g (4.4 mmol) of (S)-3-tert-butoxycarbonylamino-2-(4-isobutyrylpiperazin-1-yl)propanoic acid in 20 ml of dimethylformamide. After stirring at ambient temperature for 15 min, a solution of 500 mg (4.6 mmol) of <strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> and of 0.8 ml (4.6 mmol) of diisopropylethylamine in 10 ml of dimethylformamide is added. The reaction medium is stirred at ambient temperature for 20 h, hydrolyzed with a saturated aqueous solution of sodium hydrogen carbonate, and then diluted with ethyl acetate. The organic phase is washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated under vacuum, 1.45 g (83%) of tert-butyl [(S)-2-allyloxycarbamoyl-2-(4-isobutyrylpiperazin-1-yl)ethyl]carbamate are obtained in the form of a colorless oil. | |
83% | 1.4 g (4.4 mmol) of O-(benzotriazol-1-yl)-N,N,N?,N?-tetramethyluroniumtetrafluoroborate and then 2.3 ml (13.1 mmol) of diisopropylethylamine are added to a solution of 1.5 g (4.4 mmol) of (S)-3-tert-butoxycarbonylamino-2-(4-isobutyrylpiperazin-1-yl)propanoic acid in 20 ml of dimethylformamide. After stirring at ambient temperature for 15 min, a solution of 500 mg (4.6 mmol) of <strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> and of 0.8 ml (4.6 mmol) of diisopropylethylamine in 10 ml of dimethylformamide is added. The reaction medium is stirred at ambient temperature for 20 h, hydrolyzed with a saturated aqueous solution of sodium hydrogen carbonate, and then diluted with ethyl acetate. The organic phase is washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered, and concentrated under vacuum, 1.45 g (83%) of tert-butyl [(S)-2-allyloxycarbamoyl-2-(4-isobutyrylpiperazin-1-yl)ethyl]carbamate are obtained in the form of a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With pyridine; at 20℃;Inert atmosphere; | Synthesis of 2C-dimer O-allyl oxime 30 - The desired compound was prepared in a similar manner to dimer oxime 28 as described above, substituting O- allyl hydroxylamine hydrochloride hydrate for hydroxylamine hydrochloride. The crude product consisted of a single oxime diastereomer. Gradient elution on silica gel (0 to 40% ethyl acetate in hexanes) afforded the desired diastereomerically pure product as a colorless amorphous solid: yield (8.2 mg , 75%); XH NMR (300 MHz, CDCI3) delta 6.04 - 5.91 (m, J= 15.99, 10.61, 6.75, 5.43, 5.43, 5.18 Hz, 1 H), 5.63 (d, J = 6.85 Hz, 1 H), 5.40 (s, 1 H), 5.36 (s, 1 H), 5.26 (dd, J= 17.31, 1.71 Hz, 1 H), 5.13 (dd, J= 10.37, 1.52 Hz, 1 H), 4.62 - 4.52 (m, 2 H), 2.94 - 2.75 (m, 2 H), 2.55 (dd, J= 14.67, 8.51 Hz, 1 H), 2.46 (dd, J= 14.61 , 3.91 Hz, 1 H), 2.38 - 2.24 (m, J=13.98, 13.98, 13.73, 4.38 Hz, 2 H), 2.05 - 1.94 (m, 3 H), 1.92 - 1.84 (m, 1 H), 1.83 - 1.76 (m, 1 H), 1.76 - 1.69 (m, 2 H), 1.69 - 1.60 (m, 3 H), 1.59 - 1.50 (m, 1 H), 1.50 - 1.41 (m, 1 H), 1.39 (d, J= 4.99 Hz, 6 H), 1.36 - 1.30 (m, 2 H), 1.30 - 1.19 (m, 3 H), 0.96 (d, J = 3.57 Hz, 3 H), 0.95 (d, J= 4.1 1 Hz, 3 H), 0.91 (d, J= 7.48 Hz, 3 H), 0.79 (d, J=7.63 Hz, 2 H); ljC MR (100 MHz, CDC13) delta 159.1, 134.8, 1 16.5, 103.3, 102.2, 90.4, 90.4, 88.6, 88.5, 81.1, 80.7, 74.6, 73.9, 70.0, 52.6, 51.2, 44.9, 43.2, 37.6, 37.3, 36.7, 36.6, 34.6, 34.3, 30.3, 30.1, 29.2, 26.1, 25.7, 25.1, 24.7, 20.3, 19.9, 13.5, 12.7; ESI- HRMS m/z (M + H)+ for C35H54NO9 calc. 632.3793, found = 632.3797; FT-IR (cm 1) 2991, 2969, 2920, 1665, 1454, 1376, 1 114, 1092, 1056, 101 1, 983, 945, 880, 755; [a]D25 +50.15 (c = 0.40, CHC13). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With triethylamine; silver carbonate; In ethanol; at 50℃; for 5.33333h; | Synthetic Example 6: N'-(aryloxy)-N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetimidamide (Compound 1-507) 30 mg (0.09 mmol) of the N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroethanethioamide (1-20) synthesized by the method in Synthetic Example 4 was dissolved in 5 ml of ethanol, 50 mg (0.45 mmol) of O-ally hydroxylamine hydrochloride, 62 mul (0.45 mmol, 45 mg) of triethylamine and 25 mg (0.09 mmol) of silver carbonate were added thereto, and the resulting mixture was stirred at 50C for 5 hours and 20 minutes. After the reaction was completed, the reaction solution was returned to room temperature to filter off insoluble materials. The filtrate was concentrated under reduced pressure to perform liquid separation with ethyl acetate and 1% hydrochloric acid, then the ethyl acetate layer was washed with a saturated saline solution, and dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The ethyl acetate layer was purified by a TLC plate (one sheet of 0.5 mm plate, evolved with hexane: ethyl acetate = 1:1) to obtain the subject material. Amount obtained 15 mg (yield 45%). |
45% | With triethylamine; silver carbonate; In ethanol; at 50℃; for 5.33333h; | Synthetic Example 6: N'-(aryloxy)-N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2 (1H)-ylidene]-2.2.2-trifluoroacetimidamide (Compound1-507) 30 mg (0.09 mmol) of the N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylid ene]-2,2,2-trifluoroethanethioamide synthesized by the method in Synthetic Example 4 was dissolved in 5 ml of ethanol, 50 mg (0.45 mmol) of O-ally hydroxylamine hydrochloride, 62 mul (0.45 mmol, 45 mg) of triethylamine and 25 mg (0.09 mmol) of silver carbonate were added thereto, and the resulting mixture was stirred at 50C for 5 hours and 20 minutes. After the reaction was completed, the reaction solution was returned to room temperature to filter off insoluble materials. The filtrate was concentrated under reduced pressure to perform liquid separation with ethyl acetate and 1% hydrochloric acid, and then the ethyl acetate layer was washed with a saturated saline solution, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The ethyl acetate layer was purified by a TLC plate (one sheet of 0.5 mm plate, evolved with hexane: ethyl acetate = 1:1) to obtain the subject material. Amount obtained 15 mg (yield 45%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
> 99% | With sodium acetate; In ethanol; at 25 - 60℃; for 7h;Inert atmosphere; | 4-Allyloxyimino-4-[4-((1R,3R)-(S)-9-bicyclo[3.3.1]non-3-yl-9-aza-bicyclo[3.3.1]non-3-yl)-3-oxo-3,4-dihydro-quinoxalin-2-yl]-butyric acid ethyl ester (c23) To a solution of c21 (150 mg, 0.289 mmol) in EtOH (3 mL) was added <strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (63.2 mg, 0.577 mmol) and NaOAc (71.0 mg, 0.866 mmol) at a temperature of about 25 C. under a nitrogen atmosphere. The mixture was stirred at a temperature of about 25 C. for 5 hr and 60 C. for 2 hr. The reaction mixture was diluted with water and then extracted with CHCl3 (x3), The combined organic phases were washed with saturated aqueous NaCl, dried (Na2SO4), and concentrated. The resulting off-white amorphous solid was chromatographed (silica-gel 15 g, CHCl3/MeOH (10% concentrated NH4OH)=19/1?4/1) to provide 177.3 mg of c23 as a yellow amorphous solid. (Yield >99%). c23: 1H-NMR (300 MHz, CDCl3) delta: 1.05-1.22 (m, 2H), 1.19 (t, J=7.17 Hz, 3H), 1.39-2.12 (m, 18H), 2.33-2.51 (m, 1H), 2.63-2.82 (m, 5H), 3.47-3.60 (m, 3H), 4.06 (q, J=7.07 Hz, 2H), 4.78 (d, J=5.80 Hz, 2H), 5.24 (d, J=10.4 Hz, 1H), 5.35 (d, J=17.4 Hz, 1H), 6.05 (ddd, J=17.4, 10.4, 5.80 Hz, 1H), 7.32 (d, J=7.77 Hz, 1H), 7.53-7.66 (m, 2H), 7.92 (d, J=8.08 Hz, 1H); LC/MS: m/z=575.45 [M+H]+ (Calc: 574). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With pyridine; at 80℃; for 4h;Inert atmosphere; | After 500 mg of hydroxyphthalimide (Aldrich) was dissolved in 5 ml of dimethylformamide under argon flow, 0.3 ml of allyl iodide (Aldrich) was added, and 0.5 ml of 1,8-diazabicyclo[5.4.0]undec-7-ene (Aldrich) was slowly added. After the mixture was stirred at room temperature for 1 hour and 20 minutes, the reaction was stopped by adding a 2 N hydrochloric acid solution. The reaction liquid was diluted by adding 20 ml of ethyl acetate, followed by drying over magnesium sulfate and then filtering. The filtrate was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography using a mixture eluent of ethyl acetate/hexane (1:5) and then dried to obtain 498 mg of a compound (yield: 80%). The compound was dissolved in 5 ml of dichloromethane, and 0.11 ml of methyl hydrazine (TCI) was slowly added at 0 C. After the reaction liquid was stirred at room temperature for 2 hours, the temperature was again lowered to 0 C. The generated solid was then filtered out, and 1 ml of a 4 M-hydrochloric acid dioxane solution (Aldrich) was added to the residual filtrate, followed by filtration and drying, to obtain 236 mg of a solid (yield: 88%). 16 mg of the obtained solid and 66 mg of SAC-0906 obtained as obtained above were dissolved in 1 ml of pyridine (Aldrich) under argon flow, followed by stirring at 80 C. for 4 hours. After the temperature was lowered to room temperature, the reaction liquid was acidified by adding a 2 N hydrochloric acid solution, followed by extraction with 20 ml of diethyl ether, drying over magnesium sulfate, and filtering. The filtrate was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography using a mixed eluent of ethyl acetate/hexane (1:5) to obtain the target compound SAC-1011 (63 mg, yield: 86%). 1H-NMR (300 MHz, CDCl3) delta6.02-5.89 (m, 1H), 5.86-5.76 (m, 2H), 5.34-5.32 (m, 1H), 5.28-5.19 (m, 2H), 5.15-5.11 (m, 2H), 4.52-4.50 (m, 2H), 4.24-4.12 (m, 3H), 3.58-3.48 (m, 1H), 2.42-0.60 (m, 35H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With sodium acetate; In water; acetonitrile; at 20℃; for 6h; | To a solution of oxime 5 or 7 (314 mg, 1.00 mmol) in acetonitrile (10 mL), water (4 mL), O-benzylhydroxylamine hydrochloride (160 mg, 1.00 mmol) or <strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (112 mg, 1.00 mmol) and sodium acetate (105 mg, 1.25 mmol) were added. The mixture was stirred at room temperature for 6 h, then evaporated to half volume and extracted with dichloromethane. The organic phase was washed with water until neutral, dried over sodium sulfate and evaporated to dryness. The residue obtained was subjected to flash chromatography on a silica gel column with dichloromethane as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With sodium acetate; In water; acetonitrile; at 20℃; for 6h; | To a solution of oxime 5 or 7 (314 mg, 1.00 mmol) in acetonitrile (10 mL), water (4 mL), O-benzylhydroxylamine hydrochloride (160 mg, 1.00 mmol) or <strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (112 mg, 1.00 mmol) and sodium acetate (105 mg, 1.25 mmol) were added. The mixture was stirred at room temperature for 6 h, then evaporated to half volume and extracted with dichloromethane. The organic phase was washed with water until neutral, dried over sodium sulfate and evaporated to dryness. The residue obtained was subjected to flash chromatography on a silica gel column with dichloromethane as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With pyridine; In ethanol; for 24h;Reflux; | General procedure: Dihydropyrroloimidazol-6-one 1a (0.309 g, 1.0 mmol) and the appropriate alkoxyamine hydrochlorides or substituted benzyloxyamine hydrochlorides (2a-2n)(6 mmol) were dissolved in 15 mL of ethanol. Then, pyridines (8 mmol, 0.66 mL) were added. The reaction was heated to reflux, and the progress of the reaction was detected by TLC. After completion, the solvent was removed under reduced pressure, and the mixture was extracted with dichloromethane (3 × 20 mL). The organic layer was washed with dilute hydrochloric acid solution and then brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography (DCM : EA = 3:2) to give the pure products (3a-3n). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | General procedure: To an ice cold solution of 3 (0.39 g, 0.78 mmol) in dry DCM(25 mL), oxalyl chloride (0.40 mL, 4.70 mmol) was slowly added,and the mixture was allowed to warm to 25 C and stirred for 2 h.The solvent was removed under diminished pressure, the residuedissolved in dry THF (20 mL), and the solvent was again removed.The residue was dissolved in dry DCM (25 mL) containing NEt3(0.70 mL, 5.05 mmol), and hydroxylammonium chloride (0.20 g,2.90 mmol) was added. Stirring at 25 C was continued for another2 h. Usual aqueous workup gave a residue that was subjected tochromatography (silica gel, hexanes/ethyl acetate, 7:3), and 5(0.27 g, 68%) was obtained as a colorless solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | General procedure: To an ice cold solution of 3 (0.39 g, 0.78 mmol) in dry DCM(25 mL), oxalyl chloride (0.40 mL, 4.70 mmol) was slowly added,and the mixture was allowed to warm to 25 C and stirred for 2 h.The solvent was removed under diminished pressure, the residuedissolved in dry THF (20 mL), and the solvent was again removed.The residue was dissolved in dry DCM (25 mL) containing NEt3(0.70 mL, 5.05 mmol), and hydroxylammonium chloride (0.20 g,2.90 mmol) was added. Stirring at 25 C was continued for another2 h. Usual aqueous workup gave a residue that was subjected tochromatography (silica gel, hexanes/ethyl acetate, 7:3), and 5(0.27 g, 68%) was obtained as a colorless solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 3h; | General procedure: To a solution of propiolic acid derivatives (1 eq.) in dichloromethane (0.5 M) were added O-allyl hydroxylamine derivatives (1.2 eq.), Et3N (1.2 eq.), 4-(N,N-dimethylamino)pyridine (0.05 eq.), and EDC (1.05 eq.) at 0 C. After being stirred for 3 h at r.t., the reaction mixture was diluted with H2O and extracted with CHCl3 (3 times). The organic phase was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Hexane : EtOAc = 3 / 1) to give the corresponding hydroxamate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 3h; | General procedure: To a solution of propiolic acid derivatives (1 eq.) in dichloromethane (0.5 M) were added O-allyl hydroxylamine derivatives (1.2 eq.), Et3N (1.2 eq.), 4-(N,N-dimethylamino)pyridine (0.05 eq.), and EDC (1.05 eq.) at 0 C. After being stirred for 3 h at r.t., the reaction mixture was diluted with H2O and extracted with CHCl3 (3 times). The organic phase was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Hexane : EtOAc = 3 / 1) to give the corresponding hydroxamate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 3h; | General procedure: To a solution of propiolic acid derivatives (1 eq.) in dichloromethane (0.5 M) were added O-allyl hydroxylamine derivatives (1.2 eq.), Et3N (1.2 eq.), 4-(N,N-dimethylamino)pyridine (0.05 eq.), and EDC (1.05 eq.) at 0 C. After being stirred for 3 h at r.t., the reaction mixture was diluted with H2O and extracted with CHCl3 (3 times). The organic phase was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Hexane : EtOAc = 3 / 1) to give the corresponding hydroxamate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 3h; | General procedure: To a solution of propiolic acid derivatives (1 eq.) in dichloromethane (0.5 M) were added O-allyl hydroxylamine derivatives (1.2 eq.), Et3N (1.2 eq.), 4-(N,N-dimethylamino)pyridine (0.05 eq.), and EDC (1.05 eq.) at 0 C. After being stirred for 3 h at r.t., the reaction mixture was diluted with H2O and extracted with CHCl3 (3 times). The organic phase was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Hexane : EtOAc = 3 / 1) to give the corresponding hydroxamate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 3h; | General procedure: To a solution of propiolic acid derivatives (1 eq.) in dichloromethane (0.5 M) were added O-allyl hydroxylamine derivatives (1.2 eq.), Et3N (1.2 eq.), 4-(N,N-dimethylamino)pyridine (0.05 eq.), and EDC (1.05 eq.) at 0 C. After being stirred for 3 h at r.t., the reaction mixture was diluted with H2O and extracted with CHCl3 (3 times). The organic phase was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Hexane : EtOAc = 3 / 1) to give the corresponding hydroxamate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 3h; | General procedure: To a solution of propiolic acid derivatives (1 eq.) in dichloromethane (0.5 M) were added O-allyl hydroxylamine derivatives (1.2 eq.), Et3N (1.2 eq.), 4-(N,N-dimethylamino)pyridine (0.05 eq.), and EDC (1.05 eq.) at 0 C. After being stirred for 3 h at r.t., the reaction mixture was diluted with H2O and extracted with CHCl3 (3 times). The organic phase was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Hexane : EtOAc = 3 / 1) to give the corresponding hydroxamate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 3h; | General procedure: To a solution of propiolic acid derivatives (1 eq.) in dichloromethane (0.5 M) were added O-allyl hydroxylamine derivatives (1.2 eq.), Et3N (1.2 eq.), 4-(N,N-dimethylamino)pyridine (0.05 eq.), and EDC (1.05 eq.) at 0 C. After being stirred for 3 h at r.t., the reaction mixture was diluted with H2O and extracted with CHCl3 (3 times). The organic phase was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Hexane : EtOAc = 3 / 1) to give the corresponding hydroxamate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 3h; | General procedure: To a solution of propiolic acid derivatives (1 eq.) in dichloromethane (0.5 M) were added O-allyl hydroxylamine derivatives (1.2 eq.), Et3N (1.2 eq.), 4-(N,N-dimethylamino)pyridine (0.05 eq.), and EDC (1.05 eq.) at 0 C. After being stirred for 3 h at r.t., the reaction mixture was diluted with H2O and extracted with CHCl3 (3 times). The organic phase was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Hexane : EtOAc = 3 / 1) to give the corresponding hydroxamate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 3h; | General procedure: To a solution of propiolic acid derivatives (1 eq.) in dichloromethane (0.5 M) were added O-allyl hydroxylamine derivatives (1.2 eq.), Et3N (1.2 eq.), 4-(N,N-dimethylamino)pyridine (0.05 eq.), and EDC (1.05 eq.) at 0 C. After being stirred for 3 h at r.t., the reaction mixture was diluted with H2O and extracted with CHCl3 (3 times). The organic phase was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Hexane : EtOAc = 3 / 1) to give the corresponding hydroxamate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 3h; | General procedure: To a solution of propiolic acid derivatives (1 eq.) in dichloromethane (0.5 M) were added O-allyl hydroxylamine derivatives (1.2 eq.), Et3N (1.2 eq.), 4-(N,N-dimethylamino)pyridine (0.05 eq.), and EDC (1.05 eq.) at 0 C. After being stirred for 3 h at r.t., the reaction mixture was diluted with H2O and extracted with CHCl3 (3 times). The organic phase was dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Hexane : EtOAc = 3 / 1) to give the corresponding hydroxamate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With N,N,N,N,N,N-hexamethylphosphoric triamide; hydroxylamine hydrochloride; N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide; In N,N-dimethyl-formamide; at 30 - 40℃; for 1h;Inert atmosphere; Large scale; | Under nitrogen gas environment, the reactor was put into acetate 810kg (molecular weight 74,11.0kmol), hydroxylamine hydrochloride 500kg (molecular weight 69.5,7.2kmol), 2kgDMF, stirred for 0.5 hour, to maintain 20-30 , dropping concentration of 30 mass% sodium hydroxide solution 1000kg (7.5kmol), after the completion of dropwise addition, the reaction was kept 1 hour;After completion of the reaction, the reaction mixture was added to 2kg benzyl triethyl ammonium chloride and 970 kg of 1,3-dichloropropene (molecular weight 111,8.7kmol), was added dropwise a concentration of 30 mass% sodium hydroxide solution 1000kg (7.5kmol ), and the reaction temperature was controlled at 30-40 deg.] C, the reaction was stirred for 1 hour;To the reaction solution was added at a concentration of 30% by mass of hydrochloric acid 1000kg (8.2kmol), the reaction was warmed to 50-60 , incubated for 3 hours, the reaction was cooled to room temperature, added to a concentration of 30 mass% sodium hydroxide solution and to pH7 -, toluene was added to 500kg, and extracted three times, to the water layer, the toluene solution of hydroxylamine O- allyl chloride to give the product desolventizing 720kg hydroxylamine O- allyl chloride (molecular weight 107.5,6.7kmol), yield 93.0%, content ?99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | General procedure: To a solution of Boc-L-glutamic acid alpha-methyl ester (80 mmol) indry DMF (200 mL) were added EDCI (19.93 g; 104 mmol), HOBt(15.92 g; 104 mmol) and the reaction mixture was stirred for30 min at room temperature. Following the sequential addition ofallylamine/<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (120 mmol) andDIEA (20.68 g; 160 mmol), the reaction mixture was stirred for16 h at room temperature. Completion of the reaction was monitoredby TLC. The solvent was removed and the residue was partitionedbetween ethyl acetate (400 mL) and 5% aqueous HCl(100 mL). The layers were separated and the organic layer wasfurther washed with saturated aqueous NaHCO3 (2 x 100 mL),followed by saturated NaCl (100 mL). The organic layer was driedover anhydrous sodium sulfate, filtered and concentrated to yield ayellow-colored oily product.. 4.1.5.1. Methyl N5-allyl-N2-(tert-butoxycarbonyl)-L-glutaminate 5a.White solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With pyridine; sodium sulfate; In methanol; at 60℃; for 10h; | 2-fluoro-2- (1,2,4-triazol-1-yl) -1- [4- (trifluoromethylsulfanyl) phenyl] ethanone(279 mg, 0.914 mmol) and pyridine(0.296 mL, 3.66 mmol) in methanol (1.8 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong>(200 mg, 1.83 mmol)And anhydrous sodium sulfate (260 mg, 1.83 mmol) were added at room temperature,Followed by stirring at 60 C. for 10 hours.Water was added to the reaction solution at 0 C., and the mixture was extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 2: 1)(EZ) -2-fluoro-2- (1,2,4-triazol-1-yl)-1 - [4- (trifluoromethylsulfanyl) phenyl] ethanone O-allyl oximeOf yellow oil (267 mg, yield: 81%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With pyridine; sodium sulfate; In methanol; at 60℃; for 13h; | 1- [4- (tert-butylsulfanyl) phenyl] -2-fluoro-2- (1,2,4-triazol-1-yl) ethanone(277 mg, 0.944 mmol)And pyridine (0.305 mL, 3.77 mmol)In methanol (1.9 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (207 mg, 1.89 mmol) and anhydrous sodium sulfate (268 mg, 1.89 mmol) were added at room temperature,Followed by stirring at 60 C. for 13 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 2: 1)(EZ) -1 - [4- (tert-butylsulfanyl) phenyl]-2-fluoro-2- (1,2,4-triazol-1-yl) ethanone O-allyl oximeOf pale yellow oil (292 mg, yield: 88%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With pyridine; sodium sulfate; In methanol; at 60℃; for 7h; | 2-fluoro-1- [4- (phenylsulfanyl) phenyl] -2- (1,2,4-triazol-1-yl) ethanone(156 mg, 0.498 mmol) and pyridine (0.161 mL, 1.99 mmol)In methanol (1.7 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong>(109 mg, 0.996 mmol)And anhydrous sodium sulfate (141 mg, 0.996 mmol) were added at room temperature,Followed by stirring at 60 C. for 7 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 2: 1)(EZ) -2-fluoro-1- [4- (phenylsulfanyl) phenyl]-2- (1,2,4-triazol-1-yl) ethanone O-allyl oximeOf light brown oil (177 mg, yield: 96%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With pyridine; sodium sulfate; In methanol; at 60℃; for 6h; | 2-fluoro-2- (1,2,4-triazol-1-yl) -1- [4- (trifluoromethylsulfinyl) phenyl] ethanone(142 mg, 0.442 mmol)And pyridine (0.143 mL, 1.77 mmol) in methanol (1.5 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (96.9 mg, 0.884 mmol)And anhydrous sodium sulfate (126 mg, 0.884 mmol) were added at room temperature,Followed by stirring at 60 C. for 6 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 1: 1)(EZ) -2-fluoro-2- (1,2,4-triazol-1-yl)-1 - [4- (trifluoromethylsulfinyl) phenyl] ethanone O-allyl oximeOf pale yellow brown oil (155 mg, yield: 93%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With pyridine; sodium sulfate; In methanol; at 60℃; for 6h; | 2-fluoro-2- (1,2,4-triazol-1-yl) -1- [4- (trifluoromethylsulfonyl) phenyl] ethanone(203 mg, 0.602 mmol)And pyridine (0.195 mL, 2.41 mmol)In methanol (1.5 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong>(132 mg, 1.20 mmol)And anhydrous sodium sulfate (171 mg, 1.20 mmol) were added at room temperature,Followed by stirring at 60 C. for 6 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 1: 1)(EZ) -2-fluoro-2- (1,2,4-triazol-1-yl)-1 - [4- (trifluoromethylsulfonyl) phenyl] ethanone O-allyl oximeOf light brown oil (203 mg, yield: 86%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With pyridine; sodium sulfate; In acetonitrile; at 60℃; for 12h; | Methanesulfonic acid 4- [2-fluoro-2- (1,2,4-triazol-1-yl) acetyl] phenyl(192 mg, 0.642 mmol)And pyridine(0.208 mL, 2.56 mmol)In acetonitrile (2.1 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong>(141 mg, 1.28 mmol)And anhydrous sodium sulfate (182 mg, 1.28 mmol) were added at room temperature,And the mixture was stirred at 60 C. for 12 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 1: 2)Methanesulfonic acid 4 - [(EZ) -1-allyloxyimino-2-fluoro-2- (1,2,4-triazol-1-yl) ethyl] phenylOf a yellow solid (224 mg, yield: 98%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With pyridine; sodium sulfate; In methanol; at 60℃; for 14h; | 2-Fluoro-1- (4-isopropyloxy-3-nitrophenyl) -2- (1,2,4-triazol-1-yl) ethanone(189 mg, 0.613 mmol)To a methanol (2.0 mL) solution of pyridine (0.198 mL, 2.45 mmol)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (134 mg, 1.22 mmol) and anhydrous sodium sulfate (174 mg, 1.22 mmol) were added at room temperature,Followed by stirring at 60 C. for 14 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 1: 1)(EZ) -2-fluoro-1- (4-isopropyloxy-3-nitrophenyl) -2- (1,2,4-triazol-1-yl) ethanone O-allyl oximeOf pale brown oil (201 mg, yield: 90%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With pyridine; sodium sulfate; In methanol; at 60℃; for 18h; | 2-fluoro-2- (1,2,4-triazol-1-yl) -1- [4- (trimethylsilyl) phenyl] ethanone(227 mg, 0.818 mmol)And pyridine (0.265 mL, 3.27 mmol)In methanol (1.6 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (179 mg, 1.63 mmol) and anhydrous sodium sulfate (232 mg, 1.63 mmol) were added at room temperature,Followed by stirring at 60 C. for 18 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 8: 1 to 1: 1)(EZ) -2-fluoro-2- (1,2,4-triazol-1-yl)-1 - [4- (trimethylsilyl) phenyl] ethanone O-allyl oximeOf pale yellow oil (236 mg, yield: 86%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With pyridine; sodium sulfate; In acetonitrile; at 60℃; for 10h; | 1- [4- (tert-butyldimethylsilyloxy) phenyl] -2-fluoro-2- (1,2,4-triazol-1-yl) ethanone(125 mg, 0.372 mmol)And pyridine(0.121 mL, 1.49 mmol)In acetonitrile (1.8 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (81.6 mg, 0.745 mmol) and anhydrous sodium sulfate (106 mg, 0.745 mmol) were added at room temperature,Followed by stirring at 60 C. for 10 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 3: 1)(EZ) -1- [4- (tert-butyldimethylsilyloxy) phenyl]-2-fluoro-2- (1,2,4-triazol-1-yl) ethanone O-allyl oximeOf pale yellow oil (135 mg, yield: 92%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With pyridine; sodium sulfate; In methanol; at 60℃; for 8h; | 1- [3,4- (difluoromethylenedioxy) phenyl] -2-fluoro-2- (1,2,4-triazol-1-yl) ethanone(254 mg, 0.891 mmol)And pyridine (0.288 mL, 3.56 mmol)In methanol (1.8 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (195 mg, 1.78 mmol)And anhydrous sodium sulfate (253 mg, 1.78 mmol) were added at room temperature,Followed by stirring at 60 C. for 8 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 2: 1)(EZ) -1 - [3,4- (difluoromethylenedioxy) phenyl]-2-fluoro-2- (1,2,4-triazol-1-yl) ethanone O-allyl oxime Of pale yellow oil (260 mg, yield: 85%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With pyridine; sodium sulfate; In methanol; at 20℃; for 48h; | 1- (2,4-dichlorophenyl) -2-fluoro-2- (1,2,4-triazol-1-yl) ethanone (300 mg, 1.09 mmol)In methanol (2.18 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (240 mg, 2.18 mmol),Anhydrous sodium sulfate (310 mg, 2.18 mmol)And pyridine (0.390 mL, 4.90 mmol), and the mixture was stirred at room temperature for 48 hours. After completion of the reaction,Water was added to the reaction solution,And extracted with ethyl acetate.The combined organic layers were dried over anhydrous magnesium sulfate and concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 2: 1)(EZ) -1- (2,4-dichlorophenyl)-2-fluoro-2- (1,2,4-triazol-1-yl) ethanone O-allyl oximeOf a yellow oil (0.25 g, yield: 69%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With pyridine; sodium sulfate; In methanol; at 60℃; for 21h; | 2-fluoro-2- (1,2,4-triazol-1-yl) -1- [4- (trifluoromethyloxy) phenyl] ethanone(217 mg, 0.751 mmol)And pyridine (0.242 mL, 3.00 mmol)In methanol (1.5 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (164 mg, 1.50 mmol)And anhydrous sodium sulfate (213 mg, 1.50 mmol)At room temperature, and the mixture was stirred at 60 C. for 21 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 8: 1 to 2: 1)(EZ) -2-fluoro-2- (1,2,4-triazol-1-yl)-1 - [4- (trifluoromethyloxy) phenyl] ethanone O-allyl oximeOf pale yellow oil (246 mg, yield: 95%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With pyridine; sodium sulfate; In methanol; at 20℃; for 24h; | 2-fluoro-1- (4-fluorophenyl) -2- (1,2,4-triazol-1-yl) ethanone(300 mg, 1.34 mmol)In methanol (2.64 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong>(0.29 g, 2.68 mmol),Anhydrous sodium sulfate (380 mg, 2.68 mmol) and pyridine (0.490 mL, 6.03 mmol) were added and the mixture was stirred at room temperature for 24 hours.After completion of the reaction,Water was added to the reaction solution,And extracted with ethyl acetate.The combined organic layers were dried over anhydrous magnesium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 1: 1)(EZ) -2-fluoro-1- (4-fluorophenyl)-2- (1,2,4-triazol-1-yl) ethanone O-allyl oximeOf a yellow oil (0.32 g, yield: 85%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With pyridine; sodium sulfate; In methanol; at 60℃; for 22h; | 1- (4-bromophenyl) -2-fluoro-2- (1,2,4-triazol-1-yl) ethanone (300 mg, 1.06 mmol)In methanol (2.21 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (230 mg, 2.12 mmol),Anhydrous sodium sulfate (300 mg, 2.12 mmol)And pyridine (0.390 mL, 4.77 mmol)And the mixture was stirred at 60 C. for 22 hours.After completion of the reaction, water was added to the reaction solution at room temperature and extracted with ethyl acetate.The combined organic layers were dried over anhydrous magnesium sulfate and concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 2: 1)(EZ) -1- (4-bromophenyl) -2-fluoro-2- (1,2,4-triazol-1-yl) ethanone O-allyl oximeOf a yellow oil (280 mg, yield: 79%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With pyridine; sodium sulfate; In methanol; at 60℃; for 24h; | 1- (4-tert-butylphenyl) -2-fluoro-2- (1,2,4-triazol-1-yl) ethanone(204 mg, 0.782 mmol)And pyridine (0.252 mL, 3.12 mmol)In methanol (1.6 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (171 mg, 1.56 mmol)And anhydrous sodium sulfate (222 mg, 1.56 mmol) were added at room temperature,Followed by stirring at 60 C. for 24 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 8: 1 to 2: 1)(EZ) -1- (4-tert-butylphenyl)-2-fluoro-2- (1,2,4-triazol-1-yl) ethanone O-allyl oximeOf pale yellow oil (216 mg, yield: 87%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With pyridine; sodium sulfate; In methanol; at 60℃; for 8h; | 2-fluoro-1- (4-isopropylphenyl) -2- (1,2,4-triazol-1-yl) ethanone (83.9 mg, 0.339 mmol)And pyridine (0.110 mL, 1.35 mmol)In methanol (1.1 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (74.4 mg, 0.679 mmol)And anhydrous sodium sulfate (96.5 mg, 0.679 mmol) were added at room temperature,Followed by stirring at 60 C. for 8 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 2: 1)(EZ) -2-fluoro-1- (4-isopropylphenyl)-2- (1,2,4-triazol-1-yl) ethanone O-allyl oximeOf a tan solid (77.4 mg, yield: 75%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With pyridine; sodium sulfate; In methanol; at 60℃; for 23h; | 2-fluoro-2- (1,2,4-triazol-1-yl) -1- [4- (trifluoromethyl) phenyl] ethanone (200 mg, 0.732 mmol)In methanol (1.5 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (161 mg, 1.46 mmol),Pyridine (0.237 mL, 2.93 mmol)And anhydrous sodium sulfate (208 mg, 1.46 mmol) at room temperature, and the mixture was stirred at 60 C. for 23 hours.Water was added to the reaction solution, and the mixture was extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 5: 1 to 2: 1)(EZ) -2-fluoro-2- (1,2,4-triazol-1-yl)-1 - [4- (trifluoromethyl) phenyl] ethanone O-allyl oximeOf pale yellow oil (260 mg, yield: 95%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With pyridine; sodium sulfate; In methanol; at 60℃; for 20h; | 2-fluoro-1- [4- (methyloxymethyloxy) phenyl] -2- (1,2,4-triazol-1-yl) ethanone229 mg, 0.864 mmol)And pyridine (0.279 mL, 3.45 mmol)Of methanol (1.7 mL)To the solution <strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (189 mg, 1.72 mmol)And anhydrous sodium sulfate (245 mg, 1.72 mmol) were added at room temperature,Followed by stirring at 60 C. for 20 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 1: 1)(EZ) -2-fluoro-1- [4- (methyloxymethyloxy) phenyl] -2-(1,2,4-triazol-1-yl) ethanone O-allyl oximeOf a yellow oil (260 mg, yield: 94%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With pyridine; sodium sulfate; In methanol; at 60℃; for 8h; | 1- [4- (ethyloxy) phenyl] -2-fluoro-2- (1,2,4-triazol-1-yl) ethanone (160 mg, 0.642 mmol)And pyridine (0.208 mL, 2.57 mmol)In methanol (1.6 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (141 mg, 1.28 mmol)And anhydrous sodium sulfate (183 mg, 1.28 mmol) were added at room temperature,Followed by stirring at 60 C. for 8 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 1: 1)(EZ) -1- [4- (ethyloxy) phenyl] -2-fluoro-2-(1,2,4-triazol-1-yl) ethanone O-allyl oximeOf a tan solid (169 mg, yield: 86%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With pyridine; sodium sulfate; In methanol; at 60℃; for 12h; | 2-fluoro-1- [4- (isopropyloxy) phenyl] -2- (1,2,4-triazol-1-yl) ethanone (107 mg, 0.406 mmol)And pyridine (0.132 mL, 1.62 mmol)In methanol (1.3 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (89.1 mg, 0.813 mmol)And anhydrous sodium sulfate (116 mg, 0.813 mmol) were added at room temperature,And the mixture was stirred at 60 C. for 12 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 1: 1)(EZ) -2-fluoro-1- [4- (isopropyloxy) phenyl]-2- (1,2,4-triazol-1-yl) ethanone O-allyl oximeOf yellowish brown oil (104 mg, yield: 80%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With pyridine; sodium sulfate; In methanol; at 60℃; for 15h; | 1- [4- (difluoromethyloxy) phenyl] -2-fluoro-2- (1,2,4-triazol-1-yl) ethanone(245 mg, 0.904 mmol)And pyridine (0.292 mL, 3.61 mmol)In methanol (1.8 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (198 mg, 1.80 mmol)And anhydrous sodium sulfate (257 mg, 1.80 mmol) were added at room temperature,And the mixture was stirred at 60 C. for 15 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 1: 1)(EZ) -1- [4- (difluoromethyloxy) phenyl] -2-fluoro-2- (1,2,4-triazol-1-yl) ethanone O-Of a yellow oil (247 mg, yield: 83%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With pyridine; sodium sulfate; In methanol; at 60℃; for 11h; | 2-fluoro-1- [4- (1,1,2,2-tetrafluoroethyloxy) phenyl] -2- (1,2,4-triazol-1-yl) ethanone (268 mg, 0.834 mmol)And pyridine (0.270 mL, 3.34 mmol)In methanol (2.1 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (183 mg, 1.67 mmol)And anhydrous sodium sulfate (237 mg, 1.67 mmol) were added at room temperature,Followed by stirring at 60 C. for 11 hours.Water was added to the reaction solution at 0 C., and the mixture was extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 2: 1)(EZ) -2-fluoro-1- [4- (1,1,2,2-tetrafluoroethyloxy) phenyl] -2-(1,2,4-triazol-1-yl) ethanone O-allyl oximeOf a yellow oil (269 mg, yield: 85%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With pyridine; sodium sulfate; In methanol; at 60℃; for 7h; | 1- [4- (cyclopentyloxy) phenyl] -2-fluoro-2- (1,2,4-triazol-1-yl) ethanone(97.2 mg, 0.336 mmol)And pyridine (0.109 mL, 1.34 mmol)In methanol (1.7 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (73.2 mg, 0.672 mmol),Anhydrous sodium sulfate (95.5 mg, 0.672 mmol) was added at room temperature,Followed by stirring at 60 C. for 7 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 2: 1)(EZ) -1 - [4- (cyclopentyloxy) phenyl]-2-fluoro-2- (1,2,4-triazol-1-yl) ethanone O-allyl oximeOf yellowish brown oil (104 mg, yield: 89%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With pyridine; sodium sulfate; In methanol; at 60℃; for 7h; | 1- [4- (1,1-difluoro-2-propenyloxy) phenyl] -2-fluoro-2- (1,2,4-triazol-1-yl) ethanone(163 mg, 0.548 mmol)And pyridine (0.177 mL, 2.19 mmol)In methanol (1.8 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (120 mg, 1.09 mmol) and anhydrous sodium sulfate (156 mg, 1.09 mmol)At room temperature, and the mixture was stirred at 60 C. for 7 hours.Water was added to the reaction solution at 0 C., and the mixture was extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 2: 1)(EZ) -1- [4- (1,1-difluoro-2-propenyloxy) phenyl] -2-fluoro-(1,2,4-triazol-1-yl) ethanone O-allyl oximeOf brown oil (118 mg, yield: 61%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With pyridine; sodium sulfate; In methanol; at 60℃; for 7h; | 1- [4- (benzyloxy) phenyl] -2-fluoro-2- (1,2,4-triazol-1-yl) ethanone (183 mg, 0.588 mmol)And pyridine (0.190 mL, 2.35 mmol)In methanol (2.0 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (129 mg, 1.17 mmol)And anhydrous sodium sulfate (169 mg, 1.17 mmol) were added at room temperature,Followed by stirring at 60 C. for 7 hours.Water was added to the reaction solution at 0 C., and the mixture was extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 2: 1)(EZ) -1- [4- (benzyloxy) phenyl] -2-fluoro-2-(1,2,4-triazol-1-yl) ethanone O-allyl oximeOf pale yellow solid (215 mg, yield: 99%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With pyridine; sodium sulfate; In methanol; at 60℃; for 23h; | 1- (4-biphenylyl) -2-fluoro-2- (1,2,4-triazol-1-yl) ethanone (188 mg, 0.669 mmol)And pyridine (0.216 mL, 2.67 mmol)In methanol (1.4 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (146 mg, 1.34 mmol) and anhydrous sodium sulfate (190 mg, 1.34 mmol) were added at room temperature,Followed by stirring at 60 C. for 23 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 5: 1 to 2: 1)(EZ) -1- (4-biphenylyl) -2-fluoro-2-(1,2,4-triazol-1-yl) ethanone O-allyloxime as a pale yellow oil (221 mg, yield: 98%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With pyridine; sodium sulfate; In methanol; at 60℃; for 12h; | 2-fluoro-1- [3-fluoro-4- (phenyloxy) phenyl] -2- (1,2,4-triazol- 1 -yl) ethanone (197 mg, 0.625 mmol)And pyridine (0.202 mL, 2.50 mmol)In methanol (2.1 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (137 mg, 1.25 mmol)And anhydrous sodium sulfate (177 mg, 1.25 mmol) were added at room temperature,And the mixture was stirred at 60 C. for 12 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 2: 1)(EZ) -2-fluoro-1- [3-fluoro-4- (phenyloxy) phenyl] -2-(1,2,4-triazol-1-yl) ethanone O-allyl oximeOf the pale yellow oil (214 mg, yield: 92%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With pyridine; sodium sulfate; In methanol; at 60℃; for 6h;Inert atmosphere; | Under an argon atmosphere,Tert-butyl 4- [2-fluoro-2- (1,2,4-triazol-1-yl) acetyl] benzoate(307 mg, 1.00 mmol)And pyridine (0.325 mL, 4.02 mmol)In methanol (2.0 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (220 mg, 2.01 mmol)And anhydrous sodium sulfate (285 mg, 2.01 mmol) were added at room temperature,Followed by stirring at 60 C. for 6 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 1: 1)4 - [(EZ) -1-allyloxyimino-2-fluoro-2-(1,2,4-triazol-1-yl) ethyl] benzoateOf pale yellow oil (351 mg, yield: 97%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With pyridine; sodium sulfate; In methanol; at 60℃; for 16h; | Pivalic acid 4- [2-fluoro-2-(1,2,4-triazol-1-yl) acetyl] phenyl(227 mg, 0.744 mmol)And pyridine (0.241 mL, 2.97 mmol)In methanol (1.5 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (163 mg, 1.44 mmol)And anhydrous sodium sulfate (211 mg, 1.44 mmol)At room temperature, and the mixture was stirred at 60 C. for 16 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate,And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 10: 1 to 4: 1)Pivalic acid 4 - [(EZ) -1-allyloxyimino-2-fluoro-2-(1,2,4-triazol-1-yl) ethyl] phenylOf pale yellow solid (232 mg, yield: 86%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With pyridine; sodium sulfate; In methanol; at 60℃; for 19h; | 4- [2-fluoro-2- (1,2,4-triazol-1-yl)Acetyl] benzonitrile(300 mg, 1.30 mmol)In methanol (2.60 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (280 mg, 2.60 mmol),Anhydrous sodium sulfate (370 mg, 2.60 mmol)And pyridine (0.47 mL, 5.85 mmol)And the mixture was stirred at 60 C. for 19 hours.After completion of the reaction,Water was added to the reaction solution at room temperature,And extracted with ethyl acetate.The combined organic layers were dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 2: 1)4 - [(EZ) -1-allyloxyimino-2-fluoro-2- (1,2,4-triazol-1-yl) ethyl] benzonitrileOf a yellow solid (260 mg, yield: 70%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With pyridine; sodium sulfate; In methanol; at 60℃; for 24h; | 2-fluoro-1- [4- (methylsulfanyl) phenyl] -2- (1,2,4-triazol-1-yl) ethanone(81.9 mg, 0.326 mmol)And pyridine (0.105 mL, 1.30 mmol)In methanol (1.6 mL)<strong>[38945-21-0]O-allylhydroxylamine hydrochloride</strong> (71.5 mg, 0.652 mmol)And anhydrous sodium sulfate (92.6 mg, 0.652 mmol) were added at room temperature,Followed by stirring at 60 C. for 24 hours.Water was added to the reaction solution at 0 C.,And extracted with ethyl acetate.The organic layer was dried over anhydrous sodium sulfate, And concentrated under reduced pressure.The obtained crude product was purified by column chromatography (hexane: ethyl acetate = 8: 1 to 2: 1)(EZ) -2-fluoro-1- [4- (methylsulfanyl) phenyl]-2- (1,2,4-triazol-1-yl) ethanone O-allyl oximeOf pale yellow oil (82.6 mg, yield: 82%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.7% | With sodium acetate; In methanol; at 20℃; for 12h; | Intermediate II (300 mg, 145.6 mmol), O-allyl hydroxylamine hydrochloride (191 mg, 174.7 mmol),Anhydrous sodium acetate (143 mg, 174.7 mmol) was added to a 50 mL round bottom flask.Another 20 mL of methanol was added as a solvent, and the reaction was carried out at room temperature for 12 hours.After the reaction was completed, saturated brine was added to the round bottom flask, and the mixture was extracted with ethyl acetate (3 × 50 mL).The organic phase was dried over anhydrous sodium sulfate, and the organic phase was concentrated under reduced pressure.Intermediate III-5 (326 mg) was obtained, yield: 85.7%; oily liquid. |
Tags: 38945-21-0 synthesis path| 38945-21-0 SDS| 38945-21-0 COA| 38945-21-0 purity| 38945-21-0 application| 38945-21-0 NMR| 38945-21-0 COA| 38945-21-0 structure
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Code | Phrase |
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P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
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P322 | |
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P378 | |
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H311 | Toxic in contact with skin |
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H316 | Causes mild skin irritation |
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H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
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H362 | May cause harm to breast-fed children |
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H371 | May cause damage to organs |
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H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
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H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
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H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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