反应详情

Combine 2-chloro-6-(1-methyl-piperidin-4-yloxy)-pyridine (preparation 46, 7.0 g, 31.0 mmol), Pd2(dba)3 (1.41 g, 1.5 mmol), (±)-BINAP (1.92 g, 3.0 mmol), sodium tert-butoxide (4.15 g, 43.0 mmol), and benzophenone imine (6.9 mL, 37.0 mmol), heat at 80° C. in 200 mL of toluene. After 18 hr., cool the reaction to room temperature, and partition between ethylacetate and water. Extract with ethylacetate (1×), and methylene dichloride (2×), combine organics and dry over MgSO4, and concentrate. Dissolve residue in of 1:1 1 N aqueous HCl/THF (200 mL), stir at room temperature. After 2 hr., adjust aqueous layer to pH>10 with 5 N NaOH. Partition between ethylacetate and water, extract aqueous layer with ethylacetate (1×) and methylene dichloride three times. Combine organics, dry over MgSO4, concentrate, and further purify by chromatography (silica gel, eluting with 0-20% 2 M NH3 in methanol/ethylacetate), to obtain the title compound (6.3 g, 99% yield). Mass spectrum (ion spray): m/z=208.1 (M+1); Anal calcd for C11H17N3O.HCl.0.85H2O: Theory: C, 51.00; H, 7.67; N, 16.22. Found: C, 50.72; H, 7.27; N, 16.22.

1. temperature, cool
2. customthe reaction to room temperature
3. custompartition between ethylacetate and water
4. extractionExtract with ethylacetate (1×), and methylene dichloride (2×)
5. dry with materialdry over MgSO4
6. concentrationconcentrate
7. waitAfter 2 hr
8. customPartition between ethylacetate and water
9. extractionextract aqueous layer with ethylacetate (1×) and methylene dichloride three times
10. dry with materialCombine organics, dry over MgSO4
11. concentrationconcentrate
12. customfurther purify by chromatography (silica gel, eluting with 0-20% 2 M NH3 in methanol/ethylacetate)