Propargyl alcohol → [3-(4-Methoxyphenyl)-1,2-oxazol-5-yl]methanol

p-Anisaldehyde (3.0 g, 22 mol) was dissolved in ethanol (30 mL), and sodium bicarbonate (2.2 g, 26 mmol) was then added to the solution. The obtained mixture was stirred at room temperature, and an aqueous solution (15 mL) of hydroxylamine hydrochloride (1.7 g, 24 mmol) was then added to the reaction solution. The obtained mixture was stirred at room temperature for 1 hour. Thereafter, the reaction solution was concentrated under reduced pressure, and a sodium bicarbonate aqueous solution was then added to the residue, followed by extraction three times with ethyl acetate. The organic layer was washed with a saturated saline, and it was then dried over anhydrous sodium sulfate, followed by concentration under reduced pressure. The residue was dissolved in dimethylformamide (40 mL), and the mixture was then stirred under ice cooling. Subsequently, N-chlorosuccinimide (2.9 g, 22 mmol) was added to the reaction solution. The obtained mixture was stirred for 2.5 hours, while raising the temperature of the reaction mixture to room temperature. Thereafter, water was added to the reaction solution, and it was then extracted with ethyl acetate three times. The organic layer was washed with a saturated saline, and it was then dried over anhydrous sodium sulfate, followed by concentration under reduced pressure. The residue was purified with a fractionation purification apparatus (Biotage, ethyl acetate:hexane=2:98-2:3). The obtained chloro compound (2.5 g, 13.5 mmol) was dissolved in dichloromethane (30 mL), and propargyl alcohol (1.2 mL, 20.2 mmol) and triethylamine (2.3 mL, 16.2 mmol) were then added to the solution. The obtained mixture was stirred at room temperature for 2 hours. The reaction solution was concentrated under reduced pressure, and the residue was purified with a fractionation purification apparatus (Biotage, ethyl acetate:hexane=1:3-3:1), so as to obtain the title compound (1.8 g, 65%) in the form of a yellow solid.

1. stirringThe obtained mixture was stirred at room temperature for 1 hour
2. concentrationThereafter, the reaction solution was concentrated under reduced pressure
3. additiona sodium bicarbonate aqueous solution was then added to the residue
4. extractionfollowed by extraction three times with ethyl acetate
5. washThe organic layer was washed with a saturated saline, and it
6. dry with materialwas then dried over anhydrous sodium sulfate
7. concentrationfollowed by concentration under reduced pressure
8. dissolutionThe residue was dissolved in dimethylformamide (40 mL)
9. stirringthe mixture was then stirred under ice cooling
10. stirringThe obtained mixture was stirred for 2.5 hours
11. temperaturewhile raising the temperature of the reaction mixture to room temperature
12. extractionwas then extracted with ethyl acetate three times
13. washThe organic layer was washed with a saturated saline, and it
14. dry with materialwas then dried over anhydrous sodium sulfate
15. concentrationfollowed by concentration under reduced pressure
16. customThe residue was purified with a fractionation purification apparatus (Biotage, ethyl acetate:hexane=2:98-2:3)
17. stirringThe obtained mixture was stirred at room temperature for 2 hours
18. concentrationThe reaction solution was concentrated under reduced pressure
19. customthe residue was purified with a fractionation purification apparatus (Biotage, ethyl acetate:hexane=1:3-3:1)

ORD record

ord-5df51fbbed9b4dfa942ac9d75af90b21

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150563B2