6-Fluoroindole

beige-brown crystalline powder

Intermediate 110: 6-Fluoro-1H-indole. To a stirred suspension of (1.pound.)-(4-fluoro-2-nitrophenyl)ethanal semicarbazone (27.0 g, 0.1 10 mol) in THF (750 ml.) in a 1 L bomb was added Rh/C (5 percent; 3.5 g, 0.002 mol Rh) slurried in toluene and Fe(OAc)2 (2.9 g, 0.017 mol). The bomb was charged with H2 to 50 atm and stirred at room temperature for 2 days. The reaction mixture was filtered through celite, washing with MeOH (150 ml_). The filtrate was concentrated to give a black oil that was partitioned between DCM (500 ml.) and water (300 ml_). The layers were separated and the aqueous fraction was extracted with DCM (2 x 200 ml_). The combined organic extracts were washed with brine (200 ml_), dried (Na2SO4), and concentrated under reduced pressure. The residue was dissolved in DCM (100 ml.) and treated with flash silica to decolourise the solution. The mixture was filtered concentrated under reduced pressure, giving 12.9 g (87 percent) of the title compound. 1H NMR: (300 MHz; DMSO-d6) δ 11.1 1 (1 H, s), 7.49 (1 H, dd, J=8.6 5.5), 7.30 (1 H, t, J=2.4), 7.13 (1 H, dd, J=10.3 2.4), 6.81 (1 H, ddd, J=1 1.0, 7.6 2.4) and 6.40-6.38 (1 H, m).Example S40; Preparation of 6-fluoro-1H-indole-7-carboxylic acid; A solution of 70.3 g of 4-fluoro-1-methyl-2-nitro-benzene (453 mmol) in 330 ml DMF was treated at rt with 87.5 ml of N, N-dimethylformamide dimethylacetal (DMFDMA, 589 mmol) and 50 ml of pyrrolidine (544 mmol) and then heated in an oil bath at 115° C. under argon. The dark red solution was then cooled down to rt, and poured into 1500 ml brine, extracted twice with diethylether. The combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo, leading to 106 g residue. About half of this residue (51.5 g) were dissolved in 800 ml methanol, treated with 12.5 g 10percent Pd/C and hydrogenated at 50° C. After removal of the catalyst by filtration, the residue was purified by silicagel chromatography (800 g silicagel, heptane/EtOAc 9:1) leading to 3.5 g of 6-fluoro-1H-indole as a light green solid (5.7percent).General procedure: A mixture of compound 4a (23.5 g, 0.12 mol), copper powder (5.4 g, 0.084 mol) and quinoline (235 mL) was heated to reflux for 3 h. Upon cooling to room temperature, the filtrate was collected by filtration, diluted with ice-water and adjusted to pH 4 with concentrated hydrochloric acid, extracted with CHGeneral procedure: The aryl halide was dissolved in 5mL of methanol per mmol of (hetero)arylhalide, magnesium (5 equiv.) added and the mixture was stirred at room temperature. After completion of the reaction (between 6-12h), the reaction mixture was poured into water, acidified with dilute HCl, and extracted with ethyl acetate. The organic phase was dried over MgSO

Molecular Weight:135.14
XLogP3:2.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:135.048427358
Monoisotopic Mass:135.048427358
Topological Polar Surface Area:15.8
Heavy Atom Count:10
Complexity:126
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes