Fluorophenyl indole

A solution of 6-bromoindole (O.lOmol) in toluene (200 ml) was treated with Pd(PPh3)4 (5mol%) and stirred for 30 min. A solution of 4-fluorophenyl-boronic acid (0.25 M, 0.15 mol) in abs. EtOH was added, followed immediately by sal aq. NaHCOj (10 eq.). The biphasic mixture was refluxed for several hours and then cooled to room temperature. The reaction mixture was poured into sat. aq. NaCl (200 ml) and the layers separated. The aq. layer was extracted with additional EtOAc (200 ml) and the combined organic layers dried (Na2S04), filtered and concentrated in vacuo. The solution was filtered through silica gel using hexane-CHjCl -hexanc for elution and evaporated. Final purification by recrystallization gave the product (19 g, 90%). 

Yokoyama, M. Takahashi, M. Takashima, Y. Kohno, H. Kobayashi, H. Kataoka, K. Shidori and Y. Murakami, Chem. Fharm. Butt. 42, 832 (1994). 

Soniei, H. Ainari and Y. Makita, Chem. Pharm. Bull. 34, 3971 (1986) 

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Fluorophenyl)indol-l-ylzinc chloride 3-(Pyridin-3-yl)-l /7,3-f -pyrrolo[l, 2-c]thiazole-7-carbonyl chloride >45 [8]... 

Aminomethyl-1-methyl-5-chloro-3(o-fluorophenyl)indole HCI Chromic anhydride Ammonia Hydrogen chloride... 

A solution of 60 g of chromic anhydride in 40 ml of water was added dropwise to a suspension of 60 g of 2-aminomethyl-1 -methyl-5-chloro-3-(o-fluorophenyl)-indole hydrochloride in 600 ml of acetic acid. The mixture was stirred at room temperature overnight. To the reaction mixture was added 1.1 liters of ether and 1 liter of water and then 800 ml of 28% ammonium hydroxide, in small portions. The ethereal layer separated, washed with water, dried, and concentrated under reduced pressure. The residue (51.8 g) was dissolved in 100 ml of ethanol, and 100 ml of 20% ethanollc hydrogen chloride was added to the solution and the mixture was cooled. The precipitate was collected by filtration to yield 46.5 g of 1 -methyl-7-chloro-5-(o-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepine-2-one hydrochloride, melt-... 

Martin effected the synthesis of several 3,5-diarylated indoles by a tandem Stille-Suzuki sequence [131]. The latter reaction involves exposure of 3-(3-pyridyl)-5-bromo-l-(4-toluenesulfonyl)indole with arylboronic acids (aryl = 3-thienyl, 2-furyl, phenyl) under typical conditions to give the expected products in 86-98% yield [131], Carrera engaged 6- and 7-bromoindole in Pd-catalyzed couplings with 4-fluoro- and 4-methoxyphenylboronic acids to prepare 6- and 7-(4-fluorophenyl)indole (90% and 74% yield) and 6-(4-methoxyphenyl)indole (73% yield) [29]. Banwell and co-workers employed 7-bromoindole in a Suzuki coupling with 3,4-dioxygenated phenylboronic acids en route to the synthesis of Amaryllidaceae alkaloids [132], Yields of 7-arylated indoles are 93-99%. Moody successfully coupled 4-bromoindole... 

Chloro-l-(4-fluorophenyl)indole (6.70 kg) and 4-piperidone-monohydrate, hydrochloride (8.38 kg) were transferred to a 200 L reactor under N2 cover. Acetic acid (67 L) was added and the reaction mixture was heated to 60°C. Concentrated HCI (37%, 33.5 L) was added during 0,5 h and then the mixture was heated to the reflux temperature (85°C) and refluxed for 1 h (final temperature 95°C). After cooling to 30°C, 33.5 L acetone was added followed by further cooling to 25°C. Filtration, wash (acetone 20 L) and drying in vacuum at 60°C gave the 5-chloro-l-(4-fluorophenyl)-3-(l,2,3,6-tetrahydropyridin-4-yl)indole as a white powder, yield 8.94 kg. 

Golich, T. G., Thomsen, J. R., Green, D. L. and Jersild, J. Determination of minor impurities of (R)-l-acetoxymethyl-3-(7-[(l-N,N-dimethylcarbamoyl)-6-(4-fluorophenyl)-indol-3-oyl]-lH, 3H-pyrrolo[l,2-c]thiazol-3-yl)pyridinium chloride by high performance liquid chromatography. J. Liq. Chromatogr. 18 4107-4116, 1995. 

A soln. of 2-phenyl-3-(2-fluorophenyl) indole in glacial acetic acid ozonized to completion 2-benzamido-2 -fluorobenzophenone. Y 86.5%.— Among several reagents tried, including alkaline permanganate, chromic acid, and trifluoro-peracetic acid, ozone proved to be most successful. F. e. and methods for the prepn. of o-aminobenzophenones s. L. H. Sternbach et al., J. Org. Ghem. 27, 3781 (1962). 

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