Hydrochloric Acid → 3-(1-Benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-3-methyl-butyraldehyde

Temperature

0 °C

Step E To a mixture of methoxymethyl triphenylphosphonium chloride (12.6 g, 37 mmol) in anhydrous tetrahydrofuran (50 mL) at 0° C. was a tetrahydrofuran solution (Aldrich, 1 M) of LiHMDS (46 mL, 46 mmol) dropwise. After the addition was finished, the reaction mixture was stirred at 0° C. for 20 min. Then a tetrahydrofuran solution (40 mL) of 2-(1-benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2-methyl-propionaldehyde (5.6 g, 23 mmol) was added. The reaction mixture was stirred at 0° C. for 2 h. Water was added to quench the reaction. The mixture was extracted with ethyl acetate twice. The organic layers were combined, concentrated. The residue was dissolved into a solution of aqueous HCl solution (2 N, 50 mL, 100 mmol) and tetrahydrofuran (50 mL). The reaction mixture was heated at reflux for 30 min, then cooled to room temperature and concentrated. The residue partitioned between ethyl acetate and water. The organic layer was separated, concentrated. The residue was purified by chromatography (EtOAc:hexanes=1:3) to give 3-(1-benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-3-methyl-butyraldehyde as a yellow oil (1.65 g, 28%).

1. additionAfter the addition
2. stirringThe reaction mixture was stirred at 0° C. for 2 h
3. customto quench
4. customthe reaction
5. extractionThe mixture was extracted with ethyl acetate twice
6. concentrationconcentrated
7. temperatureThe reaction mixture was heated
8. temperatureat reflux for 30 min
9. temperaturecooled to room temperature
10. concentrationconcentrated
11. customThe residue partitioned between ethyl acetate and water
12. customThe organic layer was separated
13. concentrationconcentrated
14. customThe residue was purified by chromatography (EtOAc:hexanes=1:3)

ORD record

ord-560395e5bb3f4222a941530be01ac9c4

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08354444B2