6-Chlorooxindole

Off-white to tan crystalline powder

General procedure: TiCl4 (0.7 mL, 6 mmol)was added to a stirred suspension of Zn powder (0.78 g, 12 mmol) in freshlydistilled anhydrous THF (15 mL) at room temperature (rt) under a dry N2atmosphere. After completion of the addition, the mixture was refluxed for 2 h.The suspension of the low-valent titanium reagent thus-formed was cooled tort. A solution of isatin or its derivatives 1 or 3 (2 mmol) in THF (10 mL) wasadded dropwise. The mixture was stirred at room temperature for about 5 minunder N2. After this period, the thin layer chromatography (TLC) analysis of themixture showed the reaction completed. The reaction mixture was quenchedwith 3percent HCl (15 mL) and extracted with CHCl3 (3 50 mL). The combinedextracts were washed with water (3 50 mL) and dried over anhydrousNa2SO4. After evaporation of the solvent under reduced pressure, the crudeproduct was purified by column chromatography (petroleum ether/ethylacetate = 5:1) to give the pure products 2 or 4.Example- 4: Preparation of 6-chloro 2-oxindole (iron as reductant) 3.5L acetic acid is charged with 1 kg of dimethyl ester of 2- nitrophenylmalonate, 4.5L xylene under stirring at 25-30°C. 0.573 kg iron powder is added in lots keeping the temperature at 25-30°C. Stirring is continued when temperature reaches at 45-50°C. Reaction mass is then heated to reach at 100-105 °Ctill HPLC showed cyclized monoester to be less than lpercent.Reaction mass is gradually cooled to reach at 30-35°C and 10L water is added slowly under stirring followed by addition of 6L of con HC1 keeping the temperature below 40°C. Contents are cooled to 10- 15°C and 6-choloro 2-oxindole is collected by filtration, washed with water till free from free acid. Crude weight: 0.7kg, areapercent= 96percent, assay=93percent Crude is purified from ethyl acetate. Dry weight: 0.43kg, yield=75percent areapercent=99.91percent, assay 99.82percent , sulphated ash:0.04percentExample- 4: Preparation of 6-chloro 2-oxindole (Tin as reductant metal): 8.8 L methanol is charged with 1.1 kg dimethyl ester of 2- nitrophenylmalonate under stirring at ambient temperature followed by the addition of 4.8 L concentrated hydrochloric acid keeping the temperature in the range of 30-40°C. Contents are heated to reach at 75- 80°C till clear solution is obtained. Methanol is distilled off at 90-95°C reaction mass is compensated with 4Lwater and the reaction mass is maintained at 90-95 °C till HPLC showed malonate to be less than 2percent. Reaction mass is cooled to 45-50°C and 4L methanol is added followed by adding 0.975g tin in lots keeping the temperature in the range of 45- 50°C. Temperature is brought to 75-80°C by gradual heating and maintained for 2-3 hours. Methanol is distilled off at 90-95 °C with compensating the mass with (6.8L) 5N HC1 under stirring at 92-95 °C with HPLC monitoring for content of nitro phenyl acetic acid and nitro phenyl methyl acetate to be less than 1percent. Contents were cooled to 15- 20°C and product is filtered of, washed with water till free from acidity. Wt of crude =0.7kg, Areapercent = 96, HPLC assay= 86percent The crude mass is further purified from ethyl acetate. Dry weight = 0.5kg, yield 75percent, area: 98percent, HPLC assay 97.98percent, , sulphated ash 0.08percentGeneral procedure: Ethanol (30 mL) wasadded to 2-nitrophenylacetic acid (300 mg, 1.66 mmol) and 1, 10-phenanthroline (33 mg, 0.23 mmol) in a reaction flask. The resultant solutionwas pumped through the H-Cube Mini (5percent Pt/C, 20 C, flowrate 1.5 mL min1, H2 inlet pressure 610 bar) to near dryness. Then the reaction flask was rinsedwith ethanol (3 5 mL). The product eluant from the H-Cube was collected andconcentrated in vacuo to 1 mL, then diluted to 6 mL with ethanol. Glacialacetic acid (0.21 mL, 36.7 mmol) was added and the reaction mixture stirredovernight at room temperature. The reaction mixture was concentrated invacuo. The residue was dissolved in CH2Cl2 (10 mL) and washed with saturatedaqueous NaHCO3 (5 5 mL). The combined aqueous extracts were treated withconc. H2SO4 to pH 1 to precipitate the hydroxamic acid, which was filteredand washed with cold deionized water (10 mL).General procedure: A seal-tube (15 mL) initially fitted with a septum containing anilide 1 (0.5 mmol), Pd(OAc)2 (11.3 mg, 0.05 mmol, 10 molpercent), and AgOAc (83.5 mg, 0.5 mmol) was evacuated and purged with N2 three times. TFA (4.0 mL), and ethyl 2-iodoacetate (2a; 160 mg, 0.75 mmol) were added to the system and the reaction mixture was stirred at 120 °C for 24 h. The mixture was cooled to r.t. and filtered through a short Celite pad and washed with CH2Cl2 several times. The filtrate was concentrated under vacuum and purified on a silica gel column using hexane/EtOAc as eluent to give the corresponding pure oxindole product 3.

Molecular Weight:167.59
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:167.0137915
Monoisotopic Mass:167.0137915
Topological Polar Surface Area:29.1
Heavy Atom Count:11
Complexity:183
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes