tert-Butanol → HCID 86673332, compound

5-Formyl-2-thiophenecarboxylic acid (25 g, 160 mmol) was dissolved in tert-butyl alcohol (400 ml) and dichloromethane (100 ml), di-tert-butyl bicarbonate (42.0 g, 192 mmol), and 4-dimethylaminopyridine (2.0 g, 16 mmol) were added, and the mixture was stirred at room temperature for 3 days. The solvent was evaporated under reduced pressure, ethyl acetate was added, and the mixture was washed successively with water, 0.5N aqueous sodium hydroxide solution and saturated brine. The ethyl acetate layer was dried over anhydrous sodium sulfate. The desiccant was filtered off, and the filtrate was concentrated under reduced pressure. 5 g of the obtained residue was dissolved in tetrahydrofuran (50 ml) and methanol (5 mL), sodium borohydride (0.50 g, 13 mmol) was added at 0° C., and the mixture was stirred for 2 hours. The reaction mixture was diluted with ethyl acetate, washed successively with 0.5N hydrochloric acid and saturated brine, and dried over anhydrous sodium sulfate. The desiccant was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in dichloromethane (100 ml), and methanesulfonyl chloride (1.9 mL, 24 mmol) and N,N-diisopropylethylamine (5.7 mL, 33 mmol) were added at 0° C., and the mixture was stirred overnight. The solvent was concentrated under reduced pressure, ethyl acetate was added, and the mixture was washed successively with water and saturated brine. The ethyl acetate layer was dried over anhydrous sodium sulfate. The desiccant was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (5.3 g, 23 mmol).

1. customThe solvent was evaporated under reduced pressure, ethyl acetate
2. additionwas added
3. washthe mixture was washed successively with water, 0.5N aqueous sodium hydroxide solution and saturated brine
4. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
5. filtrationThe desiccant was filtered off
6. concentrationthe filtrate was concentrated under reduced pressure
7. dissolution5 g of the obtained residue was dissolved in tetrahydrofuran (50 ml)
8. stirringthe mixture was stirred for 2 hours
9. washwashed successively with 0.5N hydrochloric acid and saturated brine
10. dry with materialdried over anhydrous sodium sulfate
11. filtrationThe desiccant was filtered off
12. concentrationthe filtrate was concentrated under reduced pressure
13. dissolutionThe obtained residue was dissolved in dichloromethane (100 ml)
14. stirringthe mixture was stirred overnight
15. concentrationThe solvent was concentrated under reduced pressure, ethyl acetate
16. additionwas added
17. washthe mixture was washed successively with water and saturated brine
18. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
19. filtrationThe desiccant was filtered off
20. concentrationthe filtrate was concentrated under reduced pressure
21. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

ORD record

ord-0fa6fddf215c4d0aa736c68db717c92f

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09346821B2