4-BROMOOXINDOLE

To a stirred solution of 2-bromo-6-nitro-phenyl acetic acid (0.66 g, 2.54 mmol) dissolved in 50percent H2SO4 (6.0 mL)/EtOH (10.0 mL) was added Zn dust (0.66 g, 10.1 mmol) at 90° C. under N2. The reaction mixture was then treated in a manner analogous to preparation 5 to provide the intermediate title compound (0.50 g, 93percent). MS(ES) M+1 212, M+2 214.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.A mixture ofZn power (8.64g, 132.13mmol) and TiClAdd a solution of I2 (2.62g, 10. 30MMOL) in DMF (lOmL) dropwise to a solution of 4- bromoindole (2. 00G, 10. 20MMOL) and KOH (1.43g, 25. 5MMOL) in DMF (40ML). Stir for 30min at room temperature and add saturated aqueous NA2S03. STIR at room temperature for 15MIN, then dilute reaction mixture with ethyl acetate (LOOML). Wash organics three times with H20, dry organics (MGS04) and concentrate to a brown oil. Dissolve oil in 2- methoxyethanol (40ML) and heat to 100°C. Add H3PO4 (9ML) and heat to reflux for 48H. Cool to room temperature and dilute with H20 (75mL). Extract into ethyl acetate, dry (MGS04) and concentrate organics to a dark brown oil. Chromatograph on silica gel (90g), eluting with 20percent to 40percent ethyl acetate/hexanes to afford 121mg (6percent) of the title compound as a tan solid. MS (ES) 212, 214 (M+H), 210, 212 (M-H) ; HPLC shows 76percent purity.

Molecular Weight:212.04
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:210.96328
Monoisotopic Mass:210.96328
Topological Polar Surface Area:29.1
Heavy Atom Count:11
Complexity:183
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes