反应详情

50% aq NaOH (1.89 L), 2-(2,6-dichlorobenzyloxy)ethanol (473.2 g), 1,6-dibromohexane (2.44 kg, 5 eq) and tetrabutylammonium bromide (34.1 g, 5 mol %) in toluene (1.89 L) was heated to 55-60° C. for 8-20 h. On cooling water (558 mL) and toluene (558 mL) were added. The aqueous phase was separated and diluted with water (1 L) then back extracted with toluene (1.1 L). The combined toluene extracts were washed twice with water (2.2 L), then evaporated to dryness on a rotary evaporator. The excess 1,6-dibromohexane was removed using a wiped film evaporator, and the resulting crude product chromatographed on silica (5 kg Biotage), eluting with 5% ethyl acetate in petrol 60/80, to give the title compound (503.2 g)−LC RT=7.0 min.

1. additionwere added
2. customThe aqueous phase was separated
3. additiondiluted with water (1 L)
4. extractionthen back extracted with toluene (1.1 L)
5. washThe combined toluene extracts were washed twice with water (2.2 L)
6. customevaporated to dryness on a rotary evaporator
7. customThe excess 1,6-dibromohexane was removed
8. customa wiped film evaporator
9. customthe resulting crude product chromatographed on silica (5 kg Biotage)
10. washeluting with 5% ethyl acetate in petrol 60/80