5-Chlorobenzo[b]thiophene

White solid

A 25 mL round bottom flask was charged with (4-chlorophenyl)(2, 2-diethoxyethyl)sulfane (500 mg, 1.92 mmol) and chlorobenzene (2 mL). The resulting mixture was added dropwise into boiling polyphosphoric acid (1 g) in chlorobenzene (5 mL) over 5 min. Work-up: the mixture was poured over ice water (25 mL), extracted three times with EtOAc (25 mL), washed with brine (50 mL), and dried over Na(4-chlorophenyl) (2, 2-diethoxyethyl) sulfane (5 g, 19 mmol) and chlorobenzene (4 ml) were poured into a 250 ml two-necked round bottom flask, The reaction mixture was then added to a polyacrylic acid (PAA) reaction solution (5 g) obtained after boiling in chlorobenzene (5 ml). After the reaction, ice water (25 ml) was added to the mixture, and the mixture was washed with brine (50 ml) and dried over Na2S04. The mixture was chromatographed using petroleum ether to give 2.9 g of a white solid (90percent yield).[000541j To a solution of Compound 41A (500 mg, 2.97 mmol) in THF (30 mL) was added n-BuLi (1.42 ml, 3.56 mmol) at -78 C under the protection of nitrogen. Then it was stirred at -78 C for 1 h, DMF (434 mg, 5.94 mmol) was added to the mixture and stirred for another one hour at -78 C. The reaction was quenched with sat. NH4C1. After separation, the organic phase was washed with brine, and dried over anhydrous Na2SO4, and purified by silica gel column chromatography (ethyl acetate in petroleum 20% v/v) to render Compound 41B. 'H-NMR (CDC13, 400 MHz) major characteristic peaks: (5(ppm) 7.47 (dd, J= 2.0, 8.8 Hz, 1H), 7.83 (d, J= 8.8 Hz, 1H), 7.93(d, J= 2.0 Hz, 1H), 7.97 (s, 1H), 10.11 (s, 1H).EXAMPLE 33 [0221] Preparation of (2S)-3-[4-(5-Chlorobenzo[b]thiophen-2-yl)-2-methyl-1, 2, 3, 6-tetrahydropyridyl]-1-(1H-indol-4-yl)oxy-2-propanols oxalate. [CHEMMOL-00072] [0222] Preparation of 4-(5-Chlorobenzo[b]thiophen-2-yl)-2-methyl-1, 2, 3, 6-tetrahydropyridine and 4-(5-Chlorobenzo[b]thiophen-2-yl)-2-methyl-1, 2, 5, 6-tetrahydropyridine. [CHEMMOL-00073] [0223] Scheme IA, Step A: A solution of PREPARATION 20 Preparation of 5-chloro-2-(4-hydroxy-N-t-butoxycarbonylpiperidin-4-yl)benzo[b]thiophene A solution of Preparation 20 Preparation of 5-chloro-2-(4-hydroxy-N-t-butoxycarbonylpiperidin-4-yl)benzo[b]thiophene A solution of Compound 14d was converted to Compound 14e using the method described in Eur. J. Med. Chem. 2001, 36(1), 55-62). Compound 14e was oxidized with selenium dioxide, to yield Compound 14f using the method described in British patent 1399089(1971): HPLC: 3.78 min; MS (ES) m/z 239 (MH-).B. B. 5-Chlorobenzothiophene was prepared by procedures known in the art (J. Heterocyclic Chem. 1988, 25, 1271). 1.68 g (9.96 mmol) of the compound were dissolved in 20 ml dry ether, and the solution was kept under argon at room temperature, while 6.25 ml (10 mmol) of a 1.6 M solution of butyl lithium in hexane was added dropwise. It was stirred for 30 min, cooled to -30 C. followed by slow addition of 1.60 g (10.0 mmol) bromine. After 30 min stirring at this temperature cooling was stopped, and the mixture was washed with aqueous sodium thiosulfate solution. The organic layer was dried over sodium sulfate and concentrated under reduced pressure, and the title benzothiophene was obtained after chromatography on silica gel with hexane to give 1.65 g (67%) of a colorless oil, which slowly solidified.

Molecular Weight:168.64
XLogP3:3.7
Hydrogen Bond Acceptor Count:1
Exact Mass:167.9800490
Monoisotopic Mass:167.9800490
Topological Polar Surface Area:28.2
Heavy Atom Count:10
Complexity:126
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes