Methanol → HCID 59999838, compound

Temperature

40 °C

To acetic acid (250 mL) at room temperature was added Intermediate 6(a) (15.49 g, 50.79 mmol). The mixture was placed in an oil bath at 40° C. for c.a. 10 min and stirred vigorously under an Ar atmosphere until the solution went clear. Iron powder (25.34 g, 453.72 mmol) was added and the mixture was heated at 40° C. for c.a. 6 hours. The mixture was filtered through diatomaceous earth, rinsing with methanol. The combined filtrate and rinses were evaporated to give orange solids, which were determined to be a mixture of products (13.2 g) resulting from incomplete reduction of the nitro groups. This mixture (13.1 g) in CH2Cl2 (48 mL) and N,N-dimethylformamide (5 mL) was then treated with acetic anhydride (36 mL, 382 mmol) and stirred overnight under an Ar atmosphere. The CH2Cl2 was evaporated and the mixture was partitioned between ethyl acetate and saturated aqueous NaHCO3. The aqueous layer was extracted twice with ethyl acetate and the combined extracts were washed successively with 1:1 H2O:saturated aqueous NaHCO3 (multiple washings), 0.5 M aqueous HCl (X2), saturated aqueous NaHCO3 (X2) and brine. The ethyl acetate solution was then dried (Na2SO4), filtered and evaporated to give yellow solids, which were then triturated with diethyl ether (c.a. 75 mL) to give a mixture of acetylated products (11.4 g) as a yellow solids. A portion of this mixture of acetylated products (5.5 g) in acetic acid (17.4 mL) was then treated with acetic anhydride (16.5 mL, 174 mmol) and iron powder (9.74 g, 174 mmol) and heated at 40° C. under an Ar atmosphere overnight. Methanol was then added and the reaction was stirred at room temperature for c.a. 1.5 hours. Then 9:1 CH2Cl2:methanol was added, and the mixture was filtered through diatomaceous earth, rinsing with 9:1 CH2Cl2:methanol. The combined filtrate and rinses were evaporated and again methanol was added and the mixture was stirred c.a. 0.5 hours after which the methanol was evaporated. Ethyl acetate was added followed by hexane to precipitate orange solids (6.9 g) which were collected. Silica gel chromatography eluting with 1:1 acetone:hexane which afforded, after isolation, Intermediate 6(b) (4.1 g, 12.46 mmol) as a cream solid in 49% yield.

1. customThe mixture was placed in an oil bath at 40° C. for c.a
2. custom6 hours
3. filtrationThe mixture was filtered through diatomaceous earth
4. washrinsing with methanol
5. customThe combined filtrate and rinses were evaporated
6. customto give orange solids, which
7. customresulting from incomplete reduction of the nitro groups
8. stirringstirred overnight under an Ar atmosphere
9. customThe CH2Cl2 was evaporated
10. customthe mixture was partitioned between ethyl acetate and saturated aqueous NaHCO3
11. extractionThe aqueous layer was extracted twice with ethyl acetate
12. washthe combined extracts were washed successively with 1:1 H2O
13. dry with materialThe ethyl acetate solution was then dried (Na2SO4)
14. filtrationfiltered
15. customevaporated
16. customto give yellow solids, which
17. customwere then triturated with diethyl ether (c.a. 75 mL)
18. customto give
19. temperatureheated at 40° C. under an Ar atmosphere overnight
20. stirringthe reaction was stirred at room temperature for c.a
21. custom1.5 hours
22. filtrationthe mixture was filtered through diatomaceous earth
23. washrinsing with 9:1 CH2Cl2
24. customThe combined filtrate and rinses were evaporated
25. additionagain methanol was added
26. stirringthe mixture was stirred c.a
27. custom0.5 hours after which the methanol was evaporated
28. additionEthyl acetate was added
29. customto precipitate orange solids (6.9 g) which
30. customwere collected
31. washSilica gel chromatography eluting with 1:1 acetone
32. customhexane which afforded

ORD record

ord-fb7fa87f77924c14925540d60589f439

Source dataset

uspto-grants-2005_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06967198B2