Tetrahydrofuran → Benzoate hydrocodone

To a solution of hydrocodone freebase (0.596 g, 1.99 mmol) in tetrahydrofuran (25 mL) was added 1 M LiN(SiMe3)2 in tetrahydrofuran (5.98 mL). The resulting orange suspension was stirred at ambient temperatures for 30 min. after which benzoate-succinic ester (1.25 g, 5.98 mmol) was added. The resulting mixture was stirred overnight at ambient temperatures and was quenched after 18 h by the addition of 100 mL saturated ammonium chloride solution which was allowed to stir for another 2 h. Ethyl acetate (100 mL) was added to the mixture and washed with saturated ammonium chloride solution (3×100 mL) and water (1×100 mL). Organic extracts were dried over anhydrous MgSO4, solvent was removed and residue was taken up in 2-isopropanol (50 mL). Water was added until a solid formed. The resulting mixture was chilled, filtered and dried to obtain benzoate-hydrocodone freebase (0.333 g, 0.826 mmol, 42% yield) as a dark brown solid. This synthesis is depicted in FIG. 13A.

1. additionwas added
2. customwas quenched after 18 h by the addition of 100 mL saturated ammonium chloride solution which
3. stirringto stir for another 2 h
4. additionEthyl acetate (100 mL) was added to the mixture
5. washwashed with saturated ammonium chloride solution (3×100 mL) and water (1×100 mL)
6. dry with materialOrganic extracts were dried over anhydrous MgSO4, solvent
7. customwas removed
8. additionWater was added until a solid
9. customformed
10. temperatureThe resulting mixture was chilled
11. filtrationfiltered
12. customdried

ORD record

ord-c810cb130b9745ff9924c6626d192dc4

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08748413B2