Hydrochloric Acid → HCID 23078200, compound

To a dichloromethane solution (8 mL) of the compound of Example 147 (569 mg), triethylamine (303 μL) was added and the mixture was stirred for 5 min. While the mixture was chilled in an ice bath, Boc2O (358 mg) was added and the mixture was stirred for 1 hour. 4N hydrochloric acid was added to adjust the pH of the mixture to 2 to 1. This was followed by the addition of ethyl acetate and a saturated aqueous solution of sodium chloride to separate the mixture into an organic phase and an aqueous phase. The organic layer was dried over anhydrous sodium sulfate, was concentrated, and was dried in a vacuum pump to give a yellow oil. This product was dissolved in DMF (8 mL). To this solution, potassium carbonate (451 mg) and methyl iodide (135 mL) were added and the mixture was stirred at room temperature for 2 hours. The mixture was then extracted with ethyl acetate and the organic layer was dried over anhydrous sodium sulfate and was concentrated. The residue was purified on a silica gel column chromatography (hexane:ethyl acetate=3:1). While chilled in an ice bath, the resultant oil was dissolved in THF (10 mL). To this solution, lithium tetrahydroborate (40.4 mg) and ethanol (1.5 mL) were added and the mixture was stirred in an ice bath for 10 min and at room temperature for the subsequent 1 hour. Following addition of water, 4N hydrochloric acid was added to adjust the pH of the mixture to 2 to 1. Ethyl acetate and water were added to separate the mixture into an organic phase and an aqueous phase. The organic layer was dried over anhydrous sodium sulfate and was concentrated. The residue was purified on a silica gel column chromatography (hexane:ethyl acetate=1:1). Methanol hydrochloride (4 mL) was added to the resultant oil and the mixture was left overnight at room temperature. Subsequently, the solvent was removed to give the desired product as a colorless amorphous (70.0 mg).

1. temperatureWhile the mixture was chilled in an ice bath
2. stirringthe mixture was stirred for 1 hour
3. customa saturated aqueous solution of sodium chloride to separate the mixture into an organic phase
4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
5. concentrationwas concentrated
6. customwas dried in a vacuum pump
7. customto give a yellow oil
8. stirringthe mixture was stirred at room temperature for 2 hours
9. extractionThe mixture was then extracted with ethyl acetate
10. dry with materialthe organic layer was dried over anhydrous sodium sulfate
11. concentrationwas concentrated
12. customThe residue was purified on a silica gel column chromatography (hexane:ethyl acetate=3:1)
13. temperatureWhile chilled in an ice bath
14. dissolutionthe resultant oil was dissolved in THF (10 mL)
15. additionTo this solution, lithium tetrahydroborate (40.4 mg) and ethanol (1.5 mL) were added
16. stirringthe mixture was stirred in an ice bath for 10 min and at room temperature for the subsequent 1 hour
17. additionaddition of water, 4N hydrochloric acid
18. additionwas added
19. additionEthyl acetate and water were added
20. customto separate the mixture into an organic phase
21. dry with materialThe organic layer was dried over anhydrous sodium sulfate
22. concentrationwas concentrated
23. customThe residue was purified on a silica gel column chromatography (hexane:ethyl acetate=1:1)
24. additionMethanol hydrochloride (4 mL) was added to the resultant oil
25. waitthe mixture was left overnight at room temperature
26. customSubsequently, the solvent was removed

ORD record

ord-2b77550509c7417ab65384c2eef332ae

Source dataset

uspto-grants-2009_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07482491B2