反应详情

温度

28 °C

Triethylamine (315 mL, 2.26 mol) was added dropwise to formic acid (150 mL, 3.91 mol) with overhead stirring while maintaining the internal temperature below 60° C. with ice-bath cooling. Neat 4-acetylpyridine (100 mL, 0.904 mol) was then added rapidly while maintaining the temperature below 50° C. Following this addition, the reaction was allowed to cool to 28° C. and the chiral ruthenium catalyst [N-[(1R,2R)-2-(amino-N)-1,2-diphenylethyl]-2,4,6-trimethylbenzenesulfonamidato-N]chloro[(1,2,3,4,5,6-n)-1-methyl-4-(1-methylethyl)benzene]ruthenium (CAS #177552-91-9; for catalyst preparation, see: Uematsu, N.; Fujii, A.; Hashiguchi, S.; Ikariya, T.; Noyori, R.; J. Am. Chem. Soc. 1996, 118, 4916-4917) (3 g, 4.46 mmol) was added. The mixture was stirred under house vacuum for 4 h and then overnight under an atmosphere of nitrogen. The reaction mixture was added dropwise to a stirred solution of 10% Na2CO3 (4 L) and then extracted with EtOAc (3×1 L). The combined EtOAc layers were washed once with brine (1 L), treated with MgSO4 and Darco G-60 decolorizing charcoal and filtered through a 100 g plug of silica gel washing with 10% MeOH/EtOAc (1 L). The filtrate was concentrated to provide a dark oil that crystallized upon standing. The solid was dissolved in warm t-butyl methyl ether (250 mL) and the warm solution was filtered to remove a small amount of insoluble material. The filtrate was allowed to stir with cooling to room temperature and then to −15° C. The solids were collected by filtration, washing with cold t-butyl methyl ether and heptane, and then dried under high vacuum to yield (1R)-1-(4-pyridinyl)ethanol as a dark beige solid (62 g, 52.9% yield). This solid material was 96% ee based on chiral HPLC (HPLC conditions: AS-H column, 5% MeOH/CO2, 40° C., 140 bar, 2 mL/min). The filtrate was combined with the insoluble solid from the crystallization and concentrated in vacuo to yield additional (1R)-1-(4-pyridinyl)ethanol as a dark oil (37.5 g, 32% yield). This oily material was 78% ee based on chiral HPLC (see HPLC conditions above). 1H NMR (400 MHz, DMSO-d6): δ 8.47-8.43 (m, 2H), 7.32-7.28 (m, 2H), 5.37 (d, 1H, J=4.4 Hz), 4.72-4.64 (m, 1H), 1.44 (d, 3H, J=6.6 Hz).

1. temperaturewhile maintaining the internal temperature below 60° C. with ice-bath
2. temperaturecooling
3. temperaturewhile maintaining the temperature below 50° C
4. additionthis addition
5. customfor catalyst preparation
6. addition1996, 118, 4916-4917) (3 g, 4.46 mmol) was added
7. stirringThe mixture was stirred under house vacuum for 4 h
8. customovernight
9. extractionextracted with EtOAc (3×1 L)
10. washThe combined EtOAc layers were washed once with brine (1 L)
11. additiontreated with MgSO4 and Darco
12. filtrationdecolorizing charcoal and filtered through a 100 g plug of silica gel washing with 10% MeOH/EtOAc (1 L)
13. concentrationThe filtrate was concentrated
14. customto provide a dark oil that
15. customcrystallized
16. dissolutionThe solid was dissolved in warm t-butyl methyl ether (250 mL)
17. filtrationthe warm solution was filtered
18. customto remove a small amount of insoluble material
19. stirringto stir
20. temperaturewith cooling to room temperature
21. customto −15° C
22. filtrationThe solids were collected by filtration
23. washwashing with cold t-butyl methyl ether and heptane
24. customdried under high vacuum