Hydrochloric Acid → HCID 178485275, compound

Temperature

60 °C

To a mixture of toluene (100 mL), THF (20 mL) and 1 mol/L hydrochloric acid (100 mL) was added 6-[(1S)-1,3-dihydroxy-1-(1-trityl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide (10.0 g, 17.6 mmol). The reaction mixture was stirred vigorously at 60° C. for 2 hr. The reaction mixture was allowed to cool to room temperature. The aqueous layer was separated, and the obtained aqueous layer was washed twice with methyl tert-butyl ether (100 mL and 50 mL). To the obtained aqueous layer was added methanol (10 mL), and then carbonate (10.6 g) and water (10 mL) were added thereto. The obtained slurry was stirred overnight at room temperature. The obtained crystals were collected by filtration, and washed with 10% aqueous methanol. The obtained wet crystals were dried under reduced pressure to give crude crystals (5.56 g). To a mixture of methanol (30 mL) and water (3 mL) were added the crude crystals (4 g). After stirring at 50° C. for 1 hr, water (50 mL) was added to the slurry at 50° C. over 1 hr. The slurry was stirred at 50° C. for 1 hr, and then allowed to cool to room temperature. After stirring for 3 hr at room temperature, the crystals were collected by filtration and washed with water. The obtained wet crystals were dried under reduced pressure to give 6-[(1S)-1,3-dihydroxy-1-(1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide (3.69 g, 11.3 mmol). yield 89%.

1. temperatureto cool to room temperature
2. customThe aqueous layer was separated
3. washthe obtained aqueous layer was washed twice with methyl tert-butyl ether (100 mL and 50 mL)
4. additionTo the obtained aqueous layer was added methanol (10 mL)
5. additioncarbonate (10.6 g) and water (10 mL) were added
6. stirringThe obtained slurry was stirred overnight at room temperature
7. filtrationThe obtained crystals were collected by filtration
8. washwashed with 10% aqueous methanol
9. customThe obtained wet crystals were dried under reduced pressure
10. customto give crude crystals (5.56 g)
11. stirringAfter stirring at 50° C. for 1 hr
12. stirringThe slurry was stirred at 50° C. for 1 hr
13. temperatureto cool to room temperature
14. stirringAfter stirring for 3 hr at room temperature
15. filtrationthe crystals were collected by filtration
16. washwashed with water
17. customThe obtained wet crystals were dried under reduced pressure

ORD record

ord-462c82395c2243d8a897efa21aefaca3

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09278938B2