Reaction #8852

Reaction equation

ammonium chloride

propionaldehyde

tert-butyl 4-acetyl-4-methoxypiperidine-1-carboxylate

tert-Butyl 4-acetyl-4-methoxypiperidine-1-carboxylate

lithium diisopropylamine

→

title compound

Yield 55.9%

tert-Butyl 4-(3-hydroxy-1-oxopent-1-yl)-4-methoxypiperidine-1-carboxylate

Yield 55.9%

Solvents

tetrahydrofuran

Conditions

Workup

1. 1
   Extractionextracted three times with diethyl ether
2. 2
   Washwashed with saturated sodium chloride solution
3. 3
   Dryingdried over sodium sulfite
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated
6. 6
   OtherThe residue was purified by flash chromatography
7. 7
   Washeluting with 40% ethyl acetate/hexanes

Procedure

To a solution of tert-butyl 4-acetyl-4-methoxypiperidine-1-carboxylate (0.589 g, 2.29 mmol) from Step A in tetrahydrofuran (20 mL) at −78° C. was added lithium diisopropylamine (0.650 mL, 0.974 mmol) followed by propionaldehyde (0.266 g, 0.330 mL, 4.58 mmol). After 5 min, the reaction mixture was poured into saturated ammonium chloride, and extracted three times with diethyl ether. The organic layers were combined, washed with saturated sodium chloride solution, dried over sodium sulfite, filtered, and concentrated. The residue was purified by flash chromatography eluting with 40% ethyl acetate/hexanes to afford the title compound (0.404 g). MS/EI (acetonitrile/water): m/z 216.1 (M+1−BOC) retention time=2.69 min.

Source