反应详情

A stirred mixture of 48 g (0.2 mole) of 1-(diphenylmethyl)azetidin-3-ol and 22 g (0.22 mole) of triethylamine in 800 mL of toluene was cooled to 5° C. in an ice bath under nitrogen while 28 g (0.22 mole) of methanesulfonyl chloride in 30 mL of toluene was added dropwise. After stirring for 22 h, the reaction mixture was diluted with 200 mL of 2-propyl ether and 300 mL of ice water was added to dissolve the triethylamine hydrochloride formed in the reaction. The aqueous portion was separated and the organic phase washed with ice water (3×200 mL) then returned to the reaction flask. The toluene solution was treated with 39.6 g (0.22 mole) of 2-fluoro-5-(trifluoromethyl)phenol, 28.3 g (0.07 mole) of Aliquat® 336 (tricaprylymethylammonium chloride) and 26.4 g (0.66 mole) of sodium hydroxide dissolved in 50 mL of water. The mixture was stirred vigorously while heating at reflux for 24 h an stirred an additional 48 h at ambient temperature. The basic aqueous layer was then removed. The organic layer was diluted with 200 ml of isopropyl ether, washed with warm water (4×200 mL), dried over magnesium sulfate, and concentrated in vacuo to give 91.7 g of amber oil. The oil was triturated with boiling hexanes and upon cooling, 40.2 g of white crystals were obtained, mp 88°-90° C. A sample was recrystallized for analysis from hexanes yielding fine white crystals, mp 88.5°-90° C. The filtrate was concentrated to an amber oil again and when triturated with ligroin yielded an additional 9.5 g of product. The total yield was 49.7 g (62%).

1. additionwas added dropwise
2. additionwas added
3. customformed in the reaction
4. customThe aqueous portion was separated
5. washthe organic phase washed with ice water (3×200 mL)
6. stirringThe mixture was stirred vigorously
7. temperaturewhile heating
8. temperatureat reflux for 24 h
9. stirringan stirred an additional 48 h at ambient temperature
10. customThe basic aqueous layer was then removed
11. additionThe organic layer was diluted with 200 ml of isopropyl ether
12. washwashed with warm water (4×200 mL)
13. dry with materialdried over magnesium sulfate
14. concentrationconcentrated in vacuo