Water → HCID 59455550, compound

Temperature

0 °C

After methoxymethyl triphenyl phosphonium chloride (1.04 g, 3.02 mmol) was dissolved in anhydrous THF (9 mL), LiHMDS 1.0M THF solution (3 mL, 3.02 mmol) was added thereto at 0° C., and the mixture was stirred for 15 minutes. 4-Benzyloxy-3,5-difluoro-benzaldehyde (0.50 g, 2.01 mmol) obtained in Step B of Preparation Example 2 was dissolved in anhydrous THF (6 mL), and the solution was added thereto. The mixture was stirred at room temperature for 3 hours. After the termination of the reaction, the reactant was added with water, and then extracted with EtOAc. The organic layer was separated, dried with MgSO4, concentrated under reduced pressure, and then purified by column chromatography (eluent, EtOAc/Hex=1/5). After the obtained product was dissolved in THF (7.68 mL), 2N HCl (3.84 mL) was added thereto, and the mixture was stirred at 70° C. for 5 hours. After the termination of the reaction, the reactant was concentrated under reduced pressure, added with water, and then extracted with EtOAc. The organic layer was separated, dried with MgSO4, concentrated under reduced pressure, and the purified by column chromatography (eluent, EtOAc/Hex=1/5) to obtain the title compound (0.107 g, 20%).

1. additionthe solution was added
2. stirringThe mixture was stirred at room temperature for 3 hours
3. customAfter the termination of the reaction
4. extractionextracted with EtOAc
5. customThe organic layer was separated
6. dry with materialdried with MgSO4
7. concentrationconcentrated under reduced pressure
8. custompurified by column chromatography (eluent, EtOAc/Hex=1/5)
9. dissolutionAfter the obtained product was dissolved in THF (7.68 mL)
10. addition2N HCl (3.84 mL) was added
11. stirringthe mixture was stirred at 70° C. for 5 hours
12. customAfter the termination of the reaction
13. concentrationthe reactant was concentrated under reduced pressure
14. additionadded with water
15. extractionextracted with EtOAc
16. customThe organic layer was separated
17. dry with materialdried with MgSO4
18. concentrationconcentrated under reduced pressure
19. customthe purified by column chromatography (eluent, EtOAc/Hex=1/5)

ORD record

ord-2f8c46a0f79a4bfba186beb02fd029b4

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09447044B2