Dimethylformamide → 2-Thiophenemethanol, 4-(trifluoromethyl)-

温度

0 °C

To a solution of 2,2,6,6-tetramethylpiperidine (7.79 g) in THF (150 ml) was added n-butyllithium (1.6 M in hexane, 34.5 ml) at −78° C., and the mixture was stirred at 0° C. for 10 min. The solution was cooled to −78° C., and stirred for 30 min. To the solution was added 3-(trifluoromethyl)thiophene (6.99 g) in THF over 30 min, and the mixture was stirred for 1 h at same temperature. Then DMF (10.1 g) was added to the mixture, and the mixture was stirred overnight at room temperature. The mixture was quenched with 1 M HCl and extracted with EtOAc. The organic layer was separated, washed with 1 M HCl and brine successively, dried over MgSO4, concentrated in vacuo, and purified by column chromatography (hexane/EtOAc). The resulting residue was dissolved in MeOH (100 ml), and NaBH4 (0.865 g) was added to the mixture at 0° C. After stirred at room temperature for 30 min, the mixture was quenched with saturated NH4Cl solution and extracted with EtOAc. The organic layer was separated, washed with saturated NH4Cl solution and brine successively, dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography (hexane/EtOAc) to give the title compound (1.79 g) as a colorless oil.

1. temperatureThe solution was cooled to −78° C.
2. stirringstirred for 30 min
3. stirringthe mixture was stirred for 1 h at same temperature
4. stirringthe mixture was stirred overnight at room temperature
5. customThe mixture was quenched with 1 M HCl
6. extractionextracted with EtOAc
7. customThe organic layer was separated
8. washwashed with 1 M HCl and brine successively
9. dry with materialdried over MgSO4
10. concentrationconcentrated in vacuo
11. custompurified by column chromatography (hexane/EtOAc)
12. dissolutionThe resulting residue was dissolved in MeOH (100 ml)
13. additionNaBH4 (0.865 g) was added to the mixture at 0° C
14. stirringAfter stirred at room temperature for 30 min
15. customthe mixture was quenched with saturated NH4Cl solution
16. extractionextracted with EtOAc
17. customThe organic layer was separated
18. washwashed with saturated NH4Cl solution and brine successively
19. dry with materialdried over MgSO4
20. concentrationconcentrated in vacuo
21. customThe residue was purified by column chromatography (hexane/EtOAc)

ORDレコード

ord-e75a4e9910b949aa91bf5c49c663c152

出典データセット

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09365540B2