Water → (R)-4-(4-(Benzyloxy)phenyl)-1-(1-phenylethyl)-1,2,3,6-tetrahydropyridine

Temperature

32.5 °C

121.7 g crude (R)-4-(4-benzyloxy-phenyl)-1-(1-phenyl-ethyl)-piperidin-4-ol was dissolved at 40° C. in 1.21 L dichloroethane. 59.4 g (471 mmol) oxalic acid (Merck 492) was added. The mixture was boiled for 3 h, while 20 mL of water was separated. The reaction mixture was washed at room temperature with 1.2 L 10% Na2CO3. The precipitate (52 g) was separated from filtrate A and added to a mixture of 250 mL 2 N NaOH and 300 mL dichloromethane, where it was dissolved after stirring for 30 min at 30-35° C. The organic phase was separated and washed with a half-saturated NaCl solution. The resulting precipitate was separated and dissolved in 200 mL dichloromethane and 60 mL methanol. The combined organic phases were concentrated after drying over Na2SO4. 80 mL ethyl acetate was added to the residue and stirred for 2 h. The crystals were separated, washed with pentane, and dried to yield 36.5 g of (R)-4-(4-benzyloxy-phenyl)-1-(1-phenyl-ethyl)-1,2,3,6-tetrahydropyridine.

1. customwas separated
2. washThe reaction mixture was washed at room temperature with 1.2 L 10% Na2CO3
3. customThe precipitate (52 g) was separated from filtrate A
4. additionadded to a mixture of 250 mL 2 N NaOH and 300 mL dichloromethane, where it
5. dissolutionwas dissolved
6. customThe organic phase was separated
7. washwashed with a half-saturated NaCl solution
8. customThe resulting precipitate was separated
9. dissolutiondissolved in 200 mL dichloromethane
10. concentrationThe combined organic phases were concentrated
11. dry with materialafter drying over Na2SO4
12. addition80 mL ethyl acetate was added to the residue
13. stirringstirred for 2 h
14. customThe crystals were separated
15. washwashed with pentane
16. customdried

ORD record

ord-538b16c8874a44e0a8d000e571f74d39

Source dataset

uspto-grants-2001_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06274735B1