Hydrochloric Acid → HCID 178419167, compound

Under a nitrogen stream, a solution of cerium chloride (26.40 g, 3.00 equivalents) in THF (220 mL) was stirred at room temperature (25° C.) for 30 min. Sodium borohydride (4.06 g, 3.00 equivalents) was added, and the mixture was stirred at room temperature for 1.5 hrs. Then bis(m-tolyl)phosphine oxide (8.22 g, 35.7 mmol) synthesized in Reference Example 17 and lithium aluminum hydride (2.06 g, 1.22 equivalents) were successively added at −9° C. and the mixture was stirred for 3 hrs. 6M—HCl (33 mL) was added at −3° C., then water (33 mL) was added and toluene (130 mL) was added at 4° C. The mixture was stirred at room temperature for 30 min. The reaction mixture was partitioned, and the organic layer was washed successively with water (50 mL), 10% aqueous NaHCO3 solution (50 mL) and 10% aqueous NaCl solution (50 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered by gravity, and further passed through a membrane filter (0.2 μm) under reduced pressure. A borane-THF complex (36 mL, 1.02 equivalents) was added to the filtrate at around 0° C. and the mixture was stirred at room temperature for 13.5 hrs. A borane-THF complex (6.2 mL, 0.18 equivalent) was further added at room temperature, and the mixture was concentrated under reduced pressure. The residue was recrystallized from n-hexane and dried (reduced pressure, 40° C.) to give the title compound (1.70 g, white powder). yield 21%

1. additionwere successively added at −9° C.
2. stirringthe mixture was stirred for 3 hrs
3. stirringThe mixture was stirred at room temperature for 30 min
4. customThe reaction mixture was partitioned
5. washthe organic layer was washed successively with water (50 mL), 10% aqueous NaHCO3 solution (50 mL) and 10% aqueous NaCl solution (50 mL)
6. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
7. filtrationfiltered by gravity
8. filtrationfilter (0.2 μm) under reduced pressure
9. additionA borane-THF complex (36 mL, 1.02 equivalents) was added to the filtrate at around 0° C.
10. stirringthe mixture was stirred at room temperature for 13.5 hrs
11. additionA borane-THF complex (6.2 mL, 0.18 equivalent) was further added at room temperature
12. concentrationthe mixture was concentrated under reduced pressure
13. customThe residue was recrystallized from n-hexane
14. customdried (reduced pressure, 40° C.)

ORD record

ord-c4f826f905f648958ba7fdc277ebea8b

Source dataset

uspto-grants-2010_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07678942B2