Reacción #1772022

Ecuación de reacción

4-methyl-4-hydroxypiperidine

(S)-1-phenylethyl 2-bromo-2-phenylacetate

triethylamine

→

title compound

Rendimiento 60.0%

(S)-1-Phenylethyl (R)-2-(4-hydroxy-4-methylpiperidin-1-yl)-2-phenylacetate

Rendimiento 60.0%

Disolventes

ethyl acetate

THF

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGThe mixture was stirred for 1 hour at room temperature
2. 2
   Temperaturait was heated at 55-60° C. (oil bath temperature) for 4 hours
3. 3
   OtroThe cooled reaction mixture
4. 4
   Lavadowashed (H2O×2, brine)
5. 5
   Secadodried (MgSO4)
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated
8. 8
   OtroThe residue was purified by silica gel chromatography (0-60% ethyl acetate-hexane)

Procedimiento

To a solution of (S)-1-phenylethyl 2-bromo-2-phenylacetate (0.464 g, 1.45 mmol) in THF (8 mL) was added triethylamine (0.61 mL, 4.35 mmol), followed by tetrabutylammonium iodide (0.215 g, 0.58 mmol). The reaction mixture was stirred at room temperature for 5 minutes and then a solution of 4-methyl-4-hydroxypiperidine (0.251 g, 2.18 mmol) in THF (2 mL) was added. The mixture was stirred for 1 hour at room temperature and then it was heated at 55-60° C. (oil bath temperature) for 4 hours. The cooled reaction mixture was then diluted with ethyl acetate (30 mL), washed (H2O×2, brine), dried (MgSO4), filtered and concentrated. The residue was purified by silica gel chromatography (0-60% ethyl acetate-hexane) to provide first the (S,R)-isomer of the title compound (0.306 g, 60%) as a white solid and then the corresponding (S,S)-isomer (0.120 g, 23%), also as a white solid. (S,R)-isomer: 1H NMR (CD3OD) δ 7.51-7.45 (m, 2H), 7.41-7.25 (m, 8H), 5.85 (q, J=6.6 Hz, 1H), 4.05 (s, 1H), 2.56-2.45 (m, 2H), 2.41-2.29 (m, 2H), 1.71-1.49 (m, 4H), 1.38 (d, J=6.6 Hz, 3H), 1.18 (s, 3H). LCMS: Anal. Calcd. for C22H27NO3: 353. found: 354 (M+H)+. (S,S)-isomer: 1H NMR (CD3OD) δ 7.41-7.30 (m, 5H), 7.20-7.14 (m, 3H), 7.06-7.00 (m, 2H), 5.85 (q, J=6.6 Hz, 1H), 4.06 (s, 1H), 2.70-2.60 (m, 1H), 2.51 (dt, J=6.6, 3.3 Hz, 1H), 2.44-2.31 (m, 2H), 1.75-1.65 (m, 1H), 1.65-1.54 (m, 3H), 1.50 (d, J=6.8 Hz, 3H), 1.20 (s, 3H). LCMS: Anal. Calcd. for C22H27NO3: 353. found: 354 (M+H)+.

Fuente