反应详情

6.52 g (27.5 mmoles) of finely ground O-t-butyl-tyrosine (Chemical Dynamics Corp.) was placed in a 500 mL round bottom flask (oven dried) which was fitted with a condenser (oven dried). A nitrogen gas line was attached at the top of the condenser. The solid was suspended in 100 mL of dry dioxane and stirred vigorously. Diisopropylethylamine (9.04 mL, 80 mmoles) was added. Tms-Cl (6.98 mL, 55 mmoles) was added and let stir for 1 hour. Methylene chloride (200 mL) was added and the entire mixture was chilled in an ice bath. 9-Fluorenyl-methyloxycarbonyl chloride (6.47 g, 25 mmole) was added in one portion. The solution was stirred in ice for 20 minutes and warmed to room temperature for 1-1.5 hrs. The mixture was concentrated on a rotary evaporator and then distributed between 200 mL diethyl ether and 250 mL 2.5% sodium bicarbonate. The phases were separated and the aqueous layer was extracted with 2×50 mL diethyl ether. The ether layers were backwashed with 2×25 mL H2O. The combined aqueous layers were acidified to pH with 10% citric acid and extracted with 600 mL methylene chloride. The organic layers were dried over sodium sulfate, concentrated to an oil and dried by azeotroping with 2×30 mL acetonitrile. The oil solidified by pumping under high vacuum. Appropriate solvents were used to recrystallize the product. The product was found to be homogeneous (Table II).

1. custom(oven dried) which
2. customwas fitted with a condenser
3. custom(oven dried)
4. stirringlet stir for 1 hour
5. temperaturethe entire mixture was chilled in an ice bath
6. stirringThe solution was stirred in ice for 20 minutes
7. concentrationThe mixture was concentrated on a rotary evaporator
8. customThe phases were separated
9. extractionthe aqueous layer was extracted with 2×50 mL diethyl ether
10. extractionextracted with 600 mL methylene chloride
11. dry with materialThe organic layers were dried over sodium sulfate
12. concentrationconcentrated to an oil
13. customdried
14. customby azeotroping with 2×30 mL acetonitrile
15. customto recrystallize the product