Hydrochloric Acid → HCID 67337354, compound

Temperature

85 °C

Intermediate 15 (196 mg, 0.93 mmol) (prepared as described in Example 55) was dissolved into isopropanol (6 mL) in a reaction vessel and treated with 6 N HCl(aq) (310 μL, 1.9 mmol). 1-Naphthaldehyde (219 mg, 1.4 mmol) was added, the reaction vessel was sealed, and the reaction heated to 85° C. with stirring overnight. The reaction was cooled to room temperature, concentrated under reduced pressure, treated with saturated NaHCO3(aq), and extracted three times with EtOAc. The EtOAc extracts were washed with brine, combined, dried over Na2SO4, filtered, and concentrated under reduced pressure. The recovered material was eluted through a 20 gram column of silica gel with a 10.5:7:7:0.3:0.03 (750 mL) and 7:7:7:0.5:0.05 (300 mL) Hexane:MtBE:CH2Cl2:MeOH:NH4OH step gradient. The material recovered from this column was then further purified by preparative HPLC using the same conditions and method described for Example 47. The recovered material was dissolved into MeOH and treated with 2 eq. of 6 N HCl(aq). This solution was then concentrated under reduced pressure and the recovered material dissolved into hot isopropanol. After this solution had cooled to room temperature, ether was added until the solution became cloudy. This mixture was cooled to −20° C. Crystals did form and were recovered by vacuum filtration, washed with fresh ether, and dried under vacuum giving 31 mg (6.9%) of a brown solid. LC-MS: RT=5.45 min, [M+H]+=349.0.

1. customthe reaction vessel was sealed
2. temperatureThe reaction was cooled to room temperature
3. concentrationconcentrated under reduced pressure
4. additiontreated with saturated NaHCO3(aq)
5. extractionextracted three times with EtOAc
6. washThe EtOAc extracts were washed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. washThe recovered material was eluted through a 20 gram column of silica gel with a 10.5:7:7:0.3:0.03 (750 mL) and 7:7:7:0.5:0.05 (300 mL) Hexane
11. customThe material recovered from this column
12. customwas then further purified by preparative HPLC
13. dissolutionThe recovered material was dissolved into MeOH
14. concentrationThis solution was then concentrated under reduced pressure
15. dissolutionthe recovered material dissolved into hot isopropanol
16. temperatureAfter this solution had cooled to room temperature
17. additionether was added until the solution
18. temperatureThis mixture was cooled to −20° C
19. filtrationwere recovered by vacuum filtration
20. washwashed with fresh ether
21. customdried under vacuum

ORD record

ord-bba1d0efdf2443139473268bbf2398f0

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08008499B2