CHLORBENSIDE-SULFONE synthesis

Yield:-

Reaction Conditions:

in 1,2-dimethoxyethane at 70; for 6 h;

Steps:

65 Example 65: 1-Chloro-4-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulfonyl)pentyl]benzene
Example 65: 1-Chloro-4-[1-[(4-chlorophenyl)sulfonyl]-5-(methylsulfonyl)pentyl]benzene sodium 4-chlorobenzenesulfinate (211 mg, 1.06 mmol) and 4-chlorobenzyl bromide (218 mg, 1.06 mmol) were added to dimethoxyethane (5 ml), followed by stirring at 70°C for 6 hours.. After cooling to room temperature, the solvent was concentrated under reduced pressure.. The residue was added with ethyl acetate and from the resulting mixture, the insoluble matter was filtered off.. The residue obtained by concentrating the filtrate under reduced pressure was washed with hexane to yield a white powder (274 mg). Then, a toluene (10 ml) solution of the resulting white powder (61 mg), the 4-(methylsulfonyl)-1-butanol (63 mg, 0.414 mmol) obtained in Referential Example 3 and cyanomethylenetri-n-butylphosphorane (97 mg, 0.403 mmol) was heated under reflux for 20 hours under an argon atmosphere.. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure.. The residue was subjected to medium-pressure chromatography on a silica gel column, whereby from the fraction eluted with hexane:ethyl acetate(=2:3), the title compound (37 mg) was obtained as a colorless oil. IR (ATR) ν: 2931, 2871, 1581, 1492, 1475, 1411, 1394, 1276, 1139, 1085, 1012, 962, 908, 827, 752, 713, 661, 620, 566, 518, 470 cm-1.1H-NMR (400MHz, CDCl3) δ: 1.35-1.51(2H,m), 1.75-1.98(2H,m), 2.05-2.25(1H,m), 2.42-2.55(1H,m), 2.84-3.10(2H,m), 2.87(3H,s), 3.99(1H,dd,J=11.0,3.9Hz), 6.99-7.10(2H,m), 7.20-7.35(2H,m), 7.35-7.55(4H,m). MS (m/z): 435(M++H). HRMS (FAB) for C18H21O4Cl2S2 (M++H) Calculated: 435.0258 Found: 435.0240

References:

DAIICHI PHARMACEUTICAL CO., LTD. EP1466898, 2004, A1 Location in patent:Page 57

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