تفاعل #505078

معادلة التفاعل

4-methyl-4-hydroxypiperidine

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

triethylamine

→

title compound

المردود 60.0%

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

المردود 60.0%

المذيبات

ethyl acetate

THF

THF

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGThe mixture was stirred for 1 hour at room temperature
2. 2
   درجة الحرارةit was heated at 55-60° C. (oil bath temperature) for 4 hours
3. 3
   أخرىThe cooled reaction mixture
4. 4
   غسيلwashed (H2O×2, brine)
5. 5
   تجفيفdried (MgSO4)
6. 6
   ترشيحfiltered
7. 7
   تركيزconcentrated
8. 8
   أخرىThe residue was purified by silica gel chromatography (0-60% ethyl acetate-hexane)

الإجراء التجريبي

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)+.

المصدر