反应详情

To stirred solution of 3.178 g of 4-(2-ethyl-[1,3]dioxan-2-yl)-2-methoxy-pyridine-3-carbaldehyde as obtained from Example 4 (12.65 mmol) in 95 mL isopropanol and 15.8 mL water were added at 0° C. 134.6 mg sodium borohydride (3.416 mmol, 0.27 eq). The reaction was monitored by HPLC, and after 30 min (<0.2% area starting material as obtained from Example 4), the reduction was quenched by addition of 11 mL acetone and stirring was continued for 30 min at room temperature. 190 mL saturated aqueous NH4Cl were added and the mixture was extracted three times with 180 mL, in total with 540 mL dichloromethane. The combined organic phases were dried over 20 g Na2SO4 (30 min) and filtered. The solid was washed with 40 mL dichloromethane. After evaporation of solvent in a rotary evaporator (40° C./10 mbar), the crude product (3.184 g, 99% by weight) was obtained as a yellow oil. Purification was achieved by trituration with 16 mL heptane for 24 h at room temperature and subsequent standing for 4 days at −20° C. After cold filtration and removement of residual solvent in a rotary evaporator (40° C./10 mbar), the title compound (2.827 g, 11.2 mmol, 88% by weight) was obtained as white crystals.

1. additionwere added at 0° C
2. customafter 30 min (<0.2% area starting material as obtained from Example 4)
3. customthe reduction was quenched by addition of 11 mL acetone
4. addition190 mL saturated aqueous NH4Cl were added
5. extractionthe mixture was extracted three times with 180 mL
6. dry with materialThe combined organic phases were dried over 20 g Na2SO4 (30 min)
7. filtrationfiltered
8. washThe solid was washed with 40 mL dichloromethane
9. customAfter evaporation of solvent
10. customin a rotary evaporator (40° C./10 mbar)
11. customthe crude product (3.184 g, 99% by weight) was obtained as a yellow oil
12. customPurification
13. waitwas achieved by trituration with 16 mL heptane for 24 h at room temperature
14. waitsubsequent standing for 4 days at −20° C
15. filtrationAfter cold filtration and removement of residual solvent
16. customin a rotary evaporator (40° C./10 mbar)