反应详情

温度

137.5 °C

Compound 7A (about 1 mole) was combined with (R,R)-2-amino-1-cyclopentanol hydrochloride (Compound 8A, about 1.2 moles) and sodium bicarbonate (about 3 moles). To this reaction mixture was added N,N-dimethylacetamide (“DMA”), and the reaction mixture was agitated at about 135-140° C. for about 15-17 hours until complete consumption of the starting material was indicated. Compound 9A is an intermediate that is formed, but not isolated, from the reaction mixture. The reaction mixture was then cooled to about 45-50° C., and tetrabutylammonium hydroxide (about 0.05 moles of about a 40% solution in water) was charged therein, followed by methanol. The reaction mixture was refluxed at about 80-85° C. for about 8-9 hours until complete deprotection of the acetate group was indicated. The reaction mixture was cooled to about 40-45° C. and concentrated under vacuum. The pH of the reaction mixture was adjusted to about 5-6 with dilute acetic acid, and the reaction mixture was heated to about 55-65° C., and seeded with a small amount of Compound 13A. The reaction mixture was then cooled to about 30-35° C. over a period of about 2 hours, and water was added over a period of about 1 hour. The reaction mixture was further cooled to about 0-5° C. over a period of about 1 hour, and agitated at that temperature for about 4 hours. The Compound 13A product was isolated by filtration, washed with water and dried to provide about an 85-90% yield.

1. customthat is formed
2. customnot isolated, from the reaction mixture
3. temperatureThe reaction mixture was then cooled to about 45-50° C.
4. temperatureThe reaction mixture was refluxed at about 80-85° C. for about 8-9 hours until complete deprotection of the acetate group
5. temperatureThe reaction mixture was cooled to about 40-45° C.
6. concentrationconcentrated under vacuum
7. temperaturethe reaction mixture was heated to about 55-65° C.
8. temperatureThe reaction mixture was then cooled to about 30-35° C. over a period of about 2 hours
9. additionwater was added over a period of about 1 hour
10. temperatureThe reaction mixture was further cooled to about 0-5° C. over a period of about 1 hour
11. stirringagitated at that temperature for about 4 hours