反応 #1772022

反応方程式

4-methyl-4-hydroxypiperidine

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

triethylamine

→

title compound

収率 60.0%

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

収率 60.0%

溶媒

ethyl acetate

THF

THF

反応条件

後処理

1. 1
   workup.STIRRINGThe mixture was stirred for 1 hour at room temperature
2. 2
   温度it was heated at 55-60° C. (oil bath temperature) for 4 hours
3. 3
   その他The cooled reaction mixture
4. 4
   洗浄washed (H2O×2, brine)
5. 5
   乾燥dried (MgSO4)
6. 6
   ろ過filtered
7. 7
   濃縮concentrated
8. 8
   その他The residue was purified by silica gel chromatography (0-60% ethyl acetate-hexane)

実験手順

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)+.

出典