反应详情

温度

55 °C

To a suspension of the product of Step C (196 g, 0.97 mole), 4-dimethylaminopyridine (5.9 g, 0.048 mole) in dry pyridine (970 mL) at 26° C. was added dropwise over 1 hr trimethylacetylchloride (145 mL, 142.1 g, 1.18 mole, 1.2 equiv.). A slight 3° C. exotherm was noted. The reaction mixture was then heated to 55° C. for 4 hr becoming a pale yellow-orange solution. Analysis by TLC (methylene chloride: methanol (90:10), Rf (product) 0.75) showed the reaction was complete. The reaction solution was cooled to 25° C. and methanol (40 mL) was slowly added. The reaction solution was then stirred for 30 min, then concentrated in vacuo to a thick orange syrup. The residue was dissolved in methylene chloride (1.5 liters) and washed with 0.5N sodium bisulfate (3×500 mL), 1N sodium bisulfate (2×500 mL), then brine (1×500 mL). All aqueous washes were combined and extracted with methylene chloride (1×500 mL). All methylene chloride extracts were combined and dried over anhydrous sodium sulfate, then filtered and concentrated in vacuo light orange oil. The oil was suspended in toluene (200 mL) and concentrated in vacuo. The product solidified to a pale yellow solid weighing 262 g for a yield of 94%.

1. customA slight 3° C. exotherm
2. temperatureThe reaction solution was cooled to 25° C.
3. concentrationconcentrated in vacuo to a thick orange syrup
4. dissolutionThe residue was dissolved in methylene chloride (1.5 liters)
5. washwashed with 0.5N sodium bisulfate (3×500 mL), 1N sodium bisulfate (2×500 mL)
6. extractionextracted with methylene chloride (1×500 mL)
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo light orange oil
10. concentrationconcentrated in vacuo