Ethanol → 5-Cnac

Temperature

40 °C

Ethyl 8-(6-chloro-2H-1,3-benzoxazine-2,4(3H)-dionyl)octanoate (641 g, 1.7 mol) and ethyl alcohol (3200 ml) were added to a 22 liter, five neck flask. In a separate 5 liter flask, sodium hydroxide (NaOH) (288.5 g, 7.2 mol) was dissolved in deionized water (3850 ml). This mixture was added to the reaction mixture contained in the 22 liter flask. A temperature increase to 40° C. was noted. Heating of the reaction mixture was started and when the reaction temperature had increased to 50° C. it was noted that all of the solids in the reaction mixture had dissolved. A temperature of 50° C. was maintained in the reaction mixture for a period of 1.5 hours. The reaction flask was then set up for vacuum distillation. 2200 ml of distillate were collected at a vapor temperature of 55° C. (10 mm Hg) before the distillation was discontinued. The reaction flask was then placed in an ice/water bath and concentrated hydrochloric acid (HCl) (752 ml) was added over a period of 45 minutes. During this addition the reaction mixture was noted to have thickened somewhat and an additional 4 liters of deionized water was added to aid the stirring of the reaction mixture. The reaction mixture was then vacuum filtered and the filter cake was washed with 3 liters of deionized water. After drying in vacuo at room temperature 456.7 g (83.5%) of N-(5-chlorosalicyloyl)-8-aminocaprylic acid was isolated.

1. additionThis mixture was added to the reaction mixture
2. temperatureHeating of the reaction mixture
3. temperaturewhen the reaction temperature had increased to 50° C. it
4. dissolutionhad dissolved
5. temperatureA temperature of 50° C. was maintained in the reaction mixture for a period of 1.5 hours
6. distillationThe reaction flask was then set up for vacuum distillation
7. distillation2200 ml of distillate were collected at a vapor temperature of 55° C. (10 mm Hg) before the distillation
8. customThe reaction flask was then placed in an ice/water bath
9. additionconcentrated hydrochloric acid (HCl) (752 ml) was added over a period of 45 minutes
10. additionDuring this addition the reaction mixture
11. additionwas added
12. filtrationvacuum filtered
13. washthe filter cake was washed with 3 liters of deionized water
14. dry with materialAfter drying in vacuo at room temperature 456.7 g (83.5%) of N-(5-chlorosalicyloyl)-8-aminocaprylic acid
15. customwas isolated

ORD record

ord-dd0db5fd812b49139d31720c6ecfcea3

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08207227B2