反应详情

A solution of 3,5-dibromopyridine (30.45 g, 0.13 mol) in anhydrous ether (400 ml) was added dropwise to a stirred solution of n-butyllithium (1.6M in hexane, 88.3 ml) and anhydrous ether (40 ml) over 0.5 hours at -70° C. The pale yellow suspension was stirred at -70° C. for 1 hour, and a solution of 2-methoxycyclohexanone (16.5 g, 0.13 mol) in anhydrous ether (60 ml) was added dropwise. The reaction mixture was stirred at -70° C. for 2 hours and allowed to warm to room temperature. The reaction mixture was poured onto ice/water (11); sodium chloride (50 g) was added and the ether layer separated. The aqueous layer was extracted with ether (2×200ml). The combined ether layers were extracted with 2N hydrochloric acid (2×250 ml). The acid extract was washed with ether (200 ml), basified with 4N aqueous sodium hydroxide solution at room temperature (pH11), sodium chloride (50 g) was added and the precipitated oil was extracted with ether (2×400 ml). The combined extracts were dried over magnesium sulphate and concentrated in vacuo to give 2-methoxy-1-(5-bromopyrid-3-yl)cyclohexanol (30.6 g). The cyclohexanol was added in small portions to stirred sulphuric acid (114 ml). The reaction exothermed to 50° C., but no external cooling was applied. When the addition was completed after 20 minutes the red/brown solution was stirred at room temperature for 4 hours. The reaction mixture was poured onto ice/water (11) and basified to pH8 with sodium carbonate. The product was extracted with ether (2×300 ml). The ether extracts were combined, dried with magnesium sulphate and evaporated to give a pale orange oil. The oil was purified by flash chromatography over silica gel eluting with hexane/ethyl acetate 6.4 to give 2-(5-bromopyrid-3-yl)cyclohexanone (15.1 g) m.p. 67°-9° C. NMR(CDCl3). 1.6-2.1(m,4H); 2.1-2.4(m,2H); 2.4-2.6 (m,2H); 3.6-3.66(dd,1H); 7.6(s,1H); 8.18(s,1H); 8.38(s,1H).

1. customexothermed to 50° C.
2. temperatureno external cooling
3. additionWhen the addition
4. extractionThe product was extracted with ether (2×300 ml)
5. dry with materialdried with magnesium sulphate
6. customevaporated
7. customto give a pale orange oil
8. customThe oil was purified by flash chromatography over silica gel eluting with hexane/ethyl acetate 6.4