反应详情

To a 250 milliliter round bottom flask was charged 2.00 grams (6.67 mmol) of retinoic acid and 20 milliliters of CH3CN. The slurry was cooled to an external temperature of 0-10° C. while 1.0 milliliters of Et3N (7.3 mmol) was charged via syringe. To the slurry was added 0.96 milliliters (7.0 mmol) of 2,2-dimethylbutyrichloride via syringe over about 10 minutes. A thick, unstirrable slurry formed. Ten milliliters of additional CH3CN was added to improve the stirring. After about 3.5 hours, the activation was judged to be complete by HPLC analysis. To the slurry was added 2.0 milliliters of pyridine via syringe. 4-aminophenol (1.53 grams, 14.0 mmol) was then added as a solid in 2 portions over about 15 minutes. After stirring for 2 hours, the reaction was held overnight in the refrigerator (about 0-10° C.). The following morning the reaction was judged to be complete by HPLC analysis. At an external temperature of 0-10° C., 20 milliliters of 3M HCl was added dropwise over about 15 min. After stirring for about 15 minutes, about 20 milliliters of solvent was removed via rotary evaporation (45° C. bath temperature). The slurry was filtered, washed twice with 10 milliliters of water and once with 15 milliliters of heptane. The dark brown solid was dried at about 40° C. overnight on a high vacuum pump to give 2.52 grams of fenretinide (97% yield, 97% pure by area, 1.4% retinoic acid).

1. additionwas charged via syringe
2. customA thick, unstirrable slurry formed
3. waitthe reaction was held overnight in the refrigerator (about 0-10° C.)
4. stirringAfter stirring for about 15 minutes
5. customabout 20 milliliters of solvent was removed via rotary evaporation (45° C. bath temperature)
6. filtrationThe slurry was filtered
7. washwashed twice with 10 milliliters of water and once with 15 milliliters of heptane
8. customThe dark brown solid was dried at about 40° C. overnight on a high vacuum pump