* 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.
With tert.-butylnitrite; oxygen In tetrahydrofuran at 50℃; for 24 h; Schlenk technique; Inert atmosphere
General procedure: To a Schlenk tube were added oxindole 1 (0.3 mmol), t-BuONO (0.6 mmol), andTHF (2 mL). Then the tube was stirred at 50 °C under 1 atm of O2 for the indicatedtime until complete consumption of starting material monitored by TLC analysis.After the reaction was finished, the reaction mixture was washed with brine. The aqueous phase was re-extracted with ethyl acetate. The combined organic extractswere dried over Na2SO4, removal of the solvent under vacuum afforded the crudeproduct, which was purified further by column chromatography using hexane-ethylacetate.
80%
With tert.-butylhydroperoxide In 1,2-dichloro-ethane at 85℃; for 24 h; Schlenk technique
General procedure: To a Schlenk tube were added indolin-2-one 1 (0.3 mmol), t-BuOOH (0.6 mmol), and DCE (2 mL). Then the tube was stirred at 85 oC under air for the indicated time until complete consumption of starting material monitored by TLC analysis. After the reaction was finished, the reaction mixture was washed with brine. The aqueous phase was re-extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried over Na2SO4, removal of the solvent under vacuum afforded the crude product, which was purified further by column chromatography using hexane-ethyl acetate (10:1).
1-Methyl-2,5-dichloroindole-3-carbaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
1.27 g (25.4%)
In pyridine; dimefox; dichloromethane
11 EXAMPLE 11, 1-Methyl-2,5-dichloroindole-3-carbaldehyde (45)
EXAMPLE 11 1-Methyl-2,5-dichloroindole-3-carbaldehyde (45) POCl36 ml) was added dropwise to a mixture of dry DMF (5.9 ml) and dichloromethane (5.9 ml) kept at 0°C. 1-Methyl-5-chloro-1,3-dihydroindol-2-one (4.0 g) dissolved in dichloromethane (20 ml) and pyridine (2.9 ml) was added dropwise at 0°C over a period of 30 min. Subsequent stirring at room temperature for 3h. The mixture was poured onto icewater (500 ml) neutralized with NaHCO3hereafter the mixture was stirred overnight. The precipitate was filtered off, washed with water and dried. The crude material (4.45 g) was recrystallized from ethanol yielding 1.27 g (25.4%) of (45). M.p. 165-167°C. In the same way the following substituted 2-chloroindole-3-carbaldehydes were prepared: 1,5-Dimethyl-2-chloroindole-3-carbaldehyde (46)
1-Methyl-2,5-dichloroindole-3-carbaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
1.27 g (25.4%)
With pyridine; trichlorophosphate In dichloromethane; N,N-dimethyl-formamide
11 1-Methyl-2,5-dichloroindole-3-carbaldehyde (45)
EXAMPLE 11 1-Methyl-2,5-dichloroindole-3-carbaldehyde (45) POCl3 (6 ml) was added dropwise to a mixture of dry DMF (5.9 ml) and dichloromethane (5.9 ml) kept at 0° C. 1-Methyl-5-chloro-1,3-dihydroindol-2-one (4.0 g) dissolved in dichloromethane (20 ml) and pyridine (2.9 ml) was added dropwise at 0° C. over a period of 30 min. Subsequent stirring at room temperature for 3h. The mixture was poured onto icewater (500 ml) neutralized with NaHCO3 whereafter the mixture was stirred overnight. The precipitate was filtered off, washed with water and dried. The crude material (4.45 g) was recrystallized from ethanol yielding 1.27 g (25.4%) of (45). M.p. 165°-167° C. In the same way the following substituted 2-chloroindole-3-carbaldehydes were prepared:
Stage #1: oxalyl dichloride; 5-chloro-1-methylindolin-2-one In dichloromethane for 4h; Heating / reflux;
Stage #2: dimethyl amine In dichloromethane at 0℃; for 0.25h;
6.2 6.2.
6.2. 2-(2,5-dichloro-1-methyl-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide Under nitrogen, 8.1 ml (92.8 mmol) of oxalyl chloride were introduced into 150 ml of dichloromethane. Next, 3.9 g (30.7 mmol) of 5-chloro-1-methyl-1,3-dihydro-2H-indol-2-one, obtained in step 6.1. from example 6, were added in small portions. The mixture was heated under reflux for 4 h. The mixture was cooled, then concentrated under reduced pressure. The residue was dissolved under nitrogen in 120 ml of dichloromethane and the mixture was cooled to 0° C. The reaction medium was saturated with gaseous dimethylamine until a basic pH was obtained. After stirring for 15 min, the mixture was concentrated under reduced pressure. The following were added: 250 ml of dichloromethane, 100 ml of water and a 1M aqueous solution of hydrochloric acid up to a pH of 3-4. The organic phase was decanted, washed with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column with a mixture of solvents (dichloromethane/ethyl acetate: 95/5 to 50/50). 1.45 g of 2-(2,5-dichloro-1-methyl-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide were isolated in the form of a white solid. M.P.: 205-206° C.
Stage #1: 5-chloro-indolin-2-one With sodium hydride In toluene; mineral oil at 100℃; for 1h; Inert atmosphere; Sealed tube;
Stage #2: dimethyl sulfate In toluene; mineral oil at 100℃; for 2h; Inert atmosphere; Sealed tube;
With sodium hydroxide In water at 120℃; for 1.5h;
6.1 6.1.
6.1. 5-chloro-1-methyl-1,3-dihydro-2H-indol-2-one 13.3 g (0.795 mol) of 5-chloro-1,3-dihydro-2H-indol-2-one were introduced into 200 ml of water. Next, 120 ml of a 1M solution of sodium hydroxide and 11.3 ml (0.120 mol) of dimethyl sulfate were added. The mixture was heated to 120° C. for 30 min. It was left to cool, then 4.81 g (120 mmol) of sodium hydroxide and 11.3 ml (0.120 mol) of dimethyl sulfate were added. The mixture was heated to 120° C. for 30 min. It was left to cool and the operation was repeated once more. Next, the reaction mixture was filtered and the precipitate was rinsed with water and dried under vacuum in the presence of phosphorus pentoxide. 250 ml of dichloromethane were added to the filtrate. The organic phase was decanted, washed with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The precipitate was added to the residue obtained and the assembly was purified by chromatography on a neutral alumina gel column with a mixture of solvents (dichloromethane/ethyl acetate: 98/2 to 50/50). 3.9 g of 5-chloro-1-methyl-1,3-dihydro-2H-indol-2-one were isolated in the form of a white solid. M.P.: 118-119° C.
1-(5-chloro-2-hydroxy-1-methyl-1H-indol-3-yl)ethanone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
78%
With dmap at 150℃; for 4h; chemoselective reaction;
78%
With dmap at 150℃; for 4h; chemoselective reaction;
4.3. General procedure for DMAP-catalyzed acetylation of indolin-2-ones and indoline-2-thiones
General procedure: Appropriate indolin-2-one or indoline-2-thione (0.3 g) was mixed with acetic anhydride (3 mL) and 4-dimethylaminopyridine (DMAP, 1 mol %). The mixture was heated at 150 °C in a round-bottomed flask equipped with an air condenser and CaCl2 guard tube. The reaction time for each reactant is provided in [Table 2] and [Table 3]. After the completion of the reaction excess acetic anhydride was evaporated under reduced pressure. The solid residue obtained in the case of the triacetylated products was suspended in cold methanol and vacuum filtered. The product collected was thoroughly washed with hexane and dried. In the case of mono and diacetylated products the solid residue was purified using flash column chromatography (FCC) (silica gel, hexanes/ethyl acetate).
With hydrazine hydrate; potassium hydroxide; In ethylene glycol; at 100℃; for 1h;
General procedure: A mixture of substituted isatin (12.3 mmol), hydrazine hydrate (368 mmol), potassium hydroxide (245 mmol), and ethylene glycol (242 mmol) were heated at 100 C for 1 h. The reaction mixture was cooled on ice bath and acidified using concd HCl (drop wise addition) along with vigorous stirring. The precipitated product was vacuum filtered and washed with hexanes to give substituted indolin-2-ones in 90-95% yield.
With hydrazine hydrate; for 1h;Reflux;
General procedure: Step 1: To a 250 mL flask equipped with a silicone oil bubbler was added commercially available isatin (7.7 g, 50 mmol) and anhydrous DMF (80 mL). the mixture was cooled down to 0 oC. To this solution was added NaH (1.32 g, 55 mmol), followed by the addition of CH3I in 15 min. Upon completion of the reaction (monitored by TLC), the mixture was diluted with saturated NH4Cl solution and extracted with ethyl acetate. The organic layer was washed with water, dried over Na2SO4, filtered, and concentrated to yield the crude N-methylindoline-2, 3-dione, which was used directly in the next step. Step 2: The N-methylindoline-2, 3-dione (7.58 g, 47 mmol) was refluxed in NH2·NH2-H2O ( 35 %) for 1h. Then the mixture was cooled to rt. The crude product was extracted with ethyl acetate. The combined organic layer was then dried over Na2SO4, purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 10:1). 1-Methylindolin-2-one was obtained as a pink solid.
With hydrazine hydrate; at 130℃; for 3h;
General procedure: To a stirred solution of isatin 6 (20 mmol) in dry DMF (30 mL), K2CO3 (30 mmol) wasadded and stirred for 10 min. 7 (24 mmol) was added dropwise to the reaction mixture. Thereaction mixture was then stirred at room temperature overnight. Ice water was added and theprecipitate produced which was collected by filtration. Orange solid 8 was obtained afterdried by vacuum. Solid 8 was then dissolved in NH2NH2H2O (20 mL) and the reaction mixture washeated to 130 oC. After 3 h, the reaction was cooled and diluted with EtOAc. The aqueouslayer was extracted with EtOAc. The combined organic layer was washed with saturatedaqueous NaHCO3, brine, dried over anhydrous Na2SO4 and concentrated under reducedpressure. The residue 9 was used directly without purified. To a suspension of NaH in THF, N-substitued oxoindole 9 was added by portion in 0 oC.after stirred for 10 minutes, correspond isocyanate was added by potions. The mixture wascontinue stirred overnight. It was quenched by 1M HCl to adjust the PH to 2~5 and thendiluted with EtOAc. The water layer was extracted with EtOAc. The combined organic layerwas washed with water, brine, dried over anhydrous Na2SO4 and concentrated under reducedpressure. The residue was purified by column chromatography on silica gel. (PE/EA = 5/1) togive compound 1a-1r as a white solid.
Stage #1: 5-chloro-1-methylindolin-2-one With n-butyllithium; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at -78℃; for 1h;
Stage #2: chloroformic acid ethyl ester In tetrahydrofuran at -55℃; for 12h;
5.1.1.1
General procedure: 3,4,5-Trimethoxybenzaldehyde(10 mmol) was dissolved in methanol (100 mL) and treated withthe equivalent of the appropriate indolinone and piperidine (1 mL).The reaction mixture was refluxed for 1-6 h (according to a TLCtest), and the precipitate formed on cooling was collected byfiltration. Compounds 3-6, 8, 11-13 were crystallized from ethanol,7 from acetone/petroleum ether and 10 from toluene (yield 20-40% for 3, 4, 6, 7, 10-12, 14, 60-70% for 5, 8, 13). Compound 14 waspurified by column chromatography and crystallized from ethanol(yield 25%).
5.1.2. General procedure for the synthesis of compounds 4, 5, 8, 10,11, 14-16, 18-23, 25-28
General procedure: The appropriate compound 1 (10 mmol) was dissolved in methanol (100 mL) and treated with the equivalent of the appropriate aldehyde 2 and piperidine (1 mL). The reaction mixture was refluxed for 3-5 h (progress of the reaction followed by TLC), and the precipitate that formed on cooling was collected byfiltration.Compounds 16, 25 and 27 were purified by column chromatography,compounds 16 and 25 with petroleum ether/acetone, and compound 27 with methylene chloride/acetone as the eluent. All the crude products were crystallized from ethanol except compound 4 (CHCl3/MeOH) and compound 5 (acetone/petroleumether).For compounds 25-28 the yield was much lower, and an improvement was obtained by replacing piperidine with NH4OH conc.
(Z)-5-chloro-3-(hydroxy(4-(prop-1-en-2-yl)phenyl)methylene)-1-methylindolin-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
With palladium diacetate; triethylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; magnesium chloride In 1,4-dioxane at 80℃; for 19h; Inert atmosphere; Sealed tube;
(S<SUB>S</SUB>)-2-methyl-N-(2,2,2-trifluoroethylidene)-propane-2-sulfinamide[ No CAS ]
(S)-N-((S)-1-((S)-5-chloro-1-methyl-2-oxoindolin-3-yl)-2,2,2-trifluoroethyl)-2-methylpropane-2-sulfinamide[ No CAS ]
(S)-N-(1-(5-chloro-1-methyl-2-oxoindolin-3-yl)-2,2,2-trifluoroethyl)-2-methylpropane-2-sulfinamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
Stage #1: 5-chloro-1-methylindolin-2-one With lithium diisopropyl amide In hexane; dichloromethane at -78℃; for 1h; Inert atmosphere;
Stage #2: (S<SUB>S</SUB>)-2-methyl-N-(2,2,2-trifluoroethylidene)-propane-2-sulfinamide In hexane; dichloromethane at -78℃; for 5h; Inert atmosphere;
Stage #3: With ammonium chloride In hexane; dichloromethane; water at -78℃; Inert atmosphere; diastereoselective reaction;
Multi-step reaction with 2 steps
1.1: sodium hydride / mineral oil; N,N-dimethyl-formamide / 0.08 h / 0 °C / Inert atmosphere
1.2: 2 h / 0 °C / Inert atmosphere
2.1: hydrazine hydrate / 5 h / 120 °C / Inert atmosphere
Multi-step reaction with 2 steps
1.1: sodium hydride / mineral oil; N,N-dimethyl-formamide / 0.08 h / 0 °C
1.2: 0.5 h / 0 °C
2.1: hydrazine hydrate / 3 h / 130 °C
Multi-step reaction with 2 steps
1: potassium carbonate / N,N-dimethyl-formamide / 80 °C / Inert atmosphere; Sealed tube
2: hydrazine hydrate / ethanol / 24 h / 90 °C / Inert atmosphere
Multi-step reaction with 2 steps
1: potassium carbonate / N,N-dimethyl-formamide / 80 °C / Sealed tube
2: hydrazine hydrate / 6 h / 100 °C
Multi-step reaction with 2 steps
1: sodium hydride / N,N-dimethyl-formamide / 0 °C
2: hydrazine hydrate / 1 h / Reflux
Multi-step reaction with 2 steps
1: potassium carbonate / N,N-dimethyl-formamide / 12 h / 80 °C / Sealed tube
2: hydrazine hydrate / 100 °C
Multi-step reaction with 2 steps
1: potassium carbonate / N,N-dimethyl-formamide / 0 - 20 °C
2: hydrazine hydrate / Reflux
Multi-step reaction with 2 steps
1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.25 h / 0 °C / Inert atmosphere
1.2: 0 - 20 °C / Inert atmosphere
2.1: hydrazine hydrate / 3 h / 130 °C
With piperidine In methanol for 16h; Reflux; diastereoselective reaction;
General procedure for synthesis of 3-aminomethyl quaternary carbon oxindole fused five-membered carbocyclic spirooxindoles 5
General procedure: A solution of oxindole derivatives 1 (0.9mmol), phthalaldehyde 2a (0.3mmol) and piperidine (10mol%) in MeOH (6.0mL) was stirred at reflux for 16h. After completion of the reaction, as indicated by TLC, the removal of solvent and purification by flash column chromatography (hexane/EtOAc=4:1-2:1) were carried out to furnish the corresponding intermediate oxindoles 4. In an ordinary vial equipped with a magnetic stirring bar, to the mixture of the above synthetic intermediate oxindoles 4 (0.3mmol), secondary amines 3 (0.6mmol) and in 6.0mL EtOAc was added paraformaldehyde (1.2mmol). The reaction mixture was stirred at 70°C for 24h. After completion of the reaction, as indicated by TLC, the removal of solvent, purification by flash column chromatography (hexane/EtOAc=3:1-2:1) was carried out to furnish the corresponding products 5.
With tert.-butylnitrite; oxygen; In tetrahydrofuran; at 50℃; under 760.051 Torr; for 24h;Schlenk technique; Inert atmosphere;
General procedure: To a Schlenk tube were added oxindole 1 (0.3 mmol), t-BuONO (0.6 mmol), andTHF (2 mL). Then the tube was stirred at 50 C under 1 atm of O2 for the indicatedtime until complete consumption of starting material monitored by TLC analysis.After the reaction was finished, the reaction mixture was washed with brine. The aqueous phase was re-extracted with ethyl acetate. The combined organic extractswere dried over Na2SO4, removal of the solvent under vacuum afforded the crudeproduct, which was purified further by column chromatography using hexane-ethylacetate.
80%
With tert.-butylhydroperoxide; In 1,2-dichloro-ethane; at 85℃; for 24h;Schlenk technique;
General procedure: To a Schlenk tube were added indolin-2-one 1 (0.3 mmol), t-BuOOH (0.6 mmol), and DCE (2 mL). Then the tube was stirred at 85 oC under air for the indicated time until complete consumption of starting material monitored by TLC analysis. After the reaction was finished, the reaction mixture was washed with brine. The aqueous phase was re-extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried over Na2SO4, removal of the solvent under vacuum afforded the crude product, which was purified further by column chromatography using hexane-ethyl acetate (10:1).
Multi-step reaction with 3 steps
1: sodium hydride / diethyl ether / 24 h / 20 °C
2: Selectfluor / acetonitrile / 24 h / 20 °C
3: triethylamine; water / dichloromethane / 0.5 h / 20 °C
Stage #1: 5-chloro-1-methylindolin-2-one With lithium hexamethyldisilazane In tetrahydrofuran; diethyl ether at 0 - 20℃; for 1h; Inert atmosphere;
Stage #2: With chloro-trimethyl-silane In tetrahydrofuran; diethyl ether at 0 - 20℃; for 3h; Inert atmosphere;
Stage #3: With Selectfluor In acetonitrile at 0 - 20℃; Inert atmosphere;
3. Typical synthetic route for the synthesis of 3-fluorooxindole
General procedure: General Procedure: Under nitrogen atmosphere, to a stirred solution of N-substituted-2-oxindole (10 mmol) in dry Et2O (40 mL) was added LiHMDS (1.0 M in THF solution, 12 mmol, 12 mL) dropwise at 0 C. The solution was allowed to warm to ambient temperature and stirred for 1 h. Then the solution was cooled to 0 C and TMSCl (13 mmol, 1.6 mL) was added dropwise. The solution was allowed to warm to ambient temperature and stirred for another 3 h. The solvent was removed under reduced pressure, and dry MeCN (40 mL) was charged to the flask. The solution was cooled to 0 C again and Selectfluor (12 mmol, 4.3 g) was added to the solution in small portions. The resulting suspension was allowed to warm to ambient temperature and stirred overnight. The reaction was quenched by the addition of water (20 mL) and EtOAc (20 mL). The reaction mixture was extracted with EtOAc (20 mL × 2). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure Purification of the crude product was performed by flash column chromatography (Hexane/EtOAc) to afford 3-fluorooxindole.
With hydrogenchloride; [bis(acetoxy)iodo]benzene In water; 1,2-dichloro-ethane at 50℃; for 0.75h; regioselective reaction;
General Procedure for Chlorination of Arenes (GP2)
General procedure: To an 8 mL dram vial was added iodobenzene diacetate (0.6 mmol, 1.5 equiv), arene (0.4 mmol,1 eq.), dichloroethane (2 mL), then 1 M hydrochloric acid (2 mL, 5 equiv). The solution wasallowed to stir (1000 rpm) at 50 °C for the indicated amount of time. After which the solution waswashed with saturated sodium bicarbonate, followed by saturated sodium thiosulfate andconcentrated. The crude mixture was then purified by column chromatography.
5-chloro-1-methyl-2-oxo-N-phenylindoline-3-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Stage #1: 5-chloro-1-methylindolin-2-one With sodium hydride In tetrahydrofuran at 0℃; for 0.166667h;
Stage #2: phenyl isocyanate In tetrahydrofuran at 0℃;
2.1 General procedure of synthesis of 3-carboxamide oxindoles 1
General procedure: To a stirred solution of isatin 6 (20 mmol) in dry DMF (30 mL), K2CO3 (30 mmol) wasadded and stirred for 10 min. 7 (24 mmol) was added dropwise to the reaction mixture. Thereaction mixture was then stirred at room temperature overnight. Ice water was added and theprecipitate produced which was collected by filtration. Orange solid 8 was obtained afterdried by vacuum. Solid 8 was then dissolved in NH2NH2H2O (20 mL) and the reaction mixture washeated to 130 oC. After 3 h, the reaction was cooled and diluted with EtOAc. The aqueouslayer was extracted with EtOAc. The combined organic layer was washed with saturatedaqueous NaHCO3, brine, dried over anhydrous Na2SO4 and concentrated under reducedpressure. The residue 9 was used directly without purified. To a suspension of NaH in THF, N-substitued oxoindole 9 was added by portion in 0 oC.after stirred for 10 minutes, correspond isocyanate was added by potions. The mixture wascontinue stirred overnight. It was quenched by 1M HCl to adjust the PH to 2~5 and thendiluted with EtOAc. The water layer was extracted with EtOAc. The combined organic layerwas washed with water, brine, dried over anhydrous Na2SO4 and concentrated under reducedpressure. The residue was purified by column chromatography on silica gel. (PE/EA = 5/1) togive compound 1a-1r as a white solid.
With triphenylphosphine In 5,5-dimethyl-1,3-cyclohexadiene at 50℃; for 24h; Inert atmosphere;
General procedure for the P-catalyzed 3,3-disubstituted oxindoles with allenoates
General procedure: A mixture of oxindole 1 (0.30 mmol), allenoate 2 (0.75 mmol), PPh3 (0.045 mmol) in xylene (2.0 mL, dried over 4 Å MS) was stirred at 50 °C under Ar atmosphere for 24 h. After completion of the reaction (indicated by TLC), the mixture was quenched with saturated NaCl solution and diluted with EtOAc, followed by washing with H2O and saturated NaCl solution, and finally dried over Na2SO4. The crude product was purified by flash column chromatography to provide the corresponding product 3.
With [(S)-(2-phenyl-4-pheox)Ru(CH3CN)4]PF6 In dichloromethane at 20℃; for 0.0166667h; Inert atmosphere; regioselective reaction;
4.3 Typical procedure for intramolecular C-H insertion reaction of diazo-N-phenyl-N-methylacetamide [11l]
General procedure: A solution of diazoacetamides (0.2 mmol) in DCM (2.0 mL) was added to a stirred mixture of Ru(II)-Pheox catalyst (1.30 mg, 0.002 mmol) in DCM (1.0 mL) under argon atmosphere. The reaction mixture was stirred at room temperature for 1 min. Upon completion, the solvent was removed and the residue was purified by flash column chromatography on silica gel eluted with n-Hexane/EtOAc (1/3 (v/v)) to give the desired product. The regioselective ratios were determined from the crude 1H NMR spectra.
1-methyl-2,3-dihydro-5-chloro-2-oxo-N-benzyl-1H-indole-3-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
1.11 g
Stage #1: 5-chloro-1-methylindolin-2-one With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Inert atmosphere;
Stage #2: benzyl isothiocyanate In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 3.16667h; Inert atmosphere;
General procedure: To a stirred suspension of sodium hydride (6.0 mmol, 60% dispersion in mineral oil) in dry DMF (5 mL) in two-neck round-bottom flask was added 1′ (5.0 mmol) in small portions at 0 °C under argon atmosphere. The mixture was stirred for 30 minutes at 0 °C. Isocyanate (6.0 mmol) was slowly added, and this reaction was maintained at 0 °C for 10 minutes and further stirred at room temperature for 3 h (monitored by TLC). The reaction mixture was then poured into ice-cooled water (100 mL) and was acidized with HCl (1 M) to pH 4-6. The desired products 1a-1l were obtained after filtration and washed with ether (10 mL × 3).
With 5% Pd/C; Cs2CO3; tricyclohexylphosphine; Trimethylacetic acid at 140℃; for 2h; Green chemistry;
2.3 General procedure for batch reaction optimization for the synthesis of oxindole derivatives
General procedure: In a 2ml screw-capped vial equipped with a magnetic stirring bar, the N-2-bromphenylacetamide (0.2mmol, 1 eq.) was introduced, followed by PCy3 (0.02mmol, 10mol%), PivOH (0.06mmol, 0.3 eq.), Cs2CO3 (0.3mmol, 1.5 eq.) and Pd/C (0.01mmol, 5mol%). 2ml of CPME were added and the resulting mixture was stirred at 140°C for 2h. After this time, the heterogeneous mixture was filtered over a short pad of celite eluting with the same solvent used in the reaction. The solvent was removed under reduced pressure to afford the products.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
Life Science
For Research Only
100K+ Compounds
Competitive Price
1-2 Day Shipping
