Reaction #1747904

Reaction equation

3-iodomethylpiperidine-1-carboxylic acid benzyl ester

2-hydroxypyridine

NaH

→

oil

Yield 73.0%

3-(2-Oxo-2H-pyridin-1-ylmethyl)piperidine-1-carboxylic acid benzyl ester

Yield 73.0%

Solvents

DMF

Conditions

Workup

1. 1
   workup.STIRRINGThe mixture was stirred at 80° C. for 10 h
2. 2
   Temperaturecooled to room temperature
3. 3
   Otherquenched with water
4. 4
   Extractionextracted with EtOAc
5. 5
   WashThe combined organic layers were washed with brine
6. 6
   Otherdried
7. 7
   Concentrationconcentrated
8. 8
   OtherThe residue was purified by chromatography with CH2Cl2-EtOAc-MeOH (10:10:1)

Procedure

To a stirred solution of 2-hydroxypyridine (200 mg, 2 mmol) in DMF (5 mL) was added NaH (60% mixture in mineral oil, 100 mg, 2.5 mmol). The mixture was stirred at 80° C. under N2 for 2 h, and then 3-iodomethylpiperidine-1-carboxylic acid benzyl ester (720 mg, 2 mmol) was added. The mixture was stirred at 80° C. for 10 h, cooled to room temperature, quenched with water, and extracted with EtOAc. The combined organic layers were washed with brine, dried, and concentrated. The residue was purified by chromatography with CH2Cl2-EtOAc-MeOH (10:10:1) to give a viscous oil (475 mg, 73%). 1H NMR (CDCl3) δ 7.30 (m, 7H), 6.55 (d, 1H, J=9.0 Hz), 6.12 (m, 1H), 5.11 (s, 2H), 4.10-3.50 (m, 4H), 3.09 (t, 1H, J=10.2 Hz), 2.92 (dd, 1H, J=13.2, 9.0 Hz), 2.10 (m, 1H), 1.85-1.20 (m, 4H).

Source