反应 #1772025

反应方程式

piperidine

(S)-1-phenylethyl 2-(2-fluorophenyl)acetate

DBU

CBr4

→

title compound

收率 11.1%

(R)-((S)-1-Phenylethyl) 2-(2-fluorophenyl)-2-(piperidin-1-yl)acetate

收率 11.1%

溶剂

diethyl ether toluene

THF

THF

反应条件

后处理

1. 1
   温度The solution was then cooled to −78° C.
2. 2
   温度to warm to −10° C.
3. 3
   workup.STIRRINGstirred at this temperature for 2 hours
4. 4
   其他The reaction mixture was quenched with saturated aq. NH4Cl
5. 5
   其他the layers were separated
6. 6
   萃取The aqueous layer was back-extracted with ethyl acetate (2×)
7. 7
   洗涤the combined organic phases were washed (H2O, brine)
8. 8
   干燥dried (Na2SO4)
9. 9
   过滤filtered
10. 10
    浓缩concentrated in vacuo
11. 11
    workup.STIRRINGthe solution was stirred at room temperature for 24 hours
12. 12
    浓缩The volatiles were then concentrated in vacuo
13. 13
    其他the residue was purified by silica gel chromatography (Biotage/0-30% diethyl ether-hexane)
14. 14
    其他to provide

实验过程

To a solution of (S)-1-phenylethyl 2-(2-fluorophenyl)acetate (5.00 g, 19.4 mmol) in THF (1200 mL) at 0° C. was added DBU (6.19 g, 40.7 mmol) and the solution was allowed to warm to room temperature while stirring for 30 minutes. The solution was then cooled to −78° C. and a solution of CBr4 (13.5 g, 40.7 mmol) in THF (100 mL) was added and the mixture was allowed to warm to −10° C. and stirred at this temperature for 2 hours. The reaction mixture was quenched with saturated aq. NH4Cl and the layers were separated. The aqueous layer was back-extracted with ethyl acetate (2×) and the combined organic phases were washed (H2O, brine), dried (Na2SO4), filtered, and concentrated in vacuo. To the residue was added piperidine (5.73 mL, 58.1 mmol) and the solution was stirred at room temperature for 24 hours. The volatiles were then concentrated in vacuo and the residue was purified by silica gel chromatography (Biotage/0-30% diethyl ether-hexane) to provide a pure mixture of diastereomers (2:1 ratio by 1H NMR) as a yellow oil (2.07 g, 31%), along with unreacted starting material (2.53 g, 51%). Further chromatography of the diastereomeric mixture (Biotage/0-10% diethyl ether-toluene) provided the title compound as a colorless oil (0.737 g, 11%). 1H NMR (400 MHz, CD3OD) δ 7.52 (ddd, J=9.4, 7.6, 1.8 Hz, 1H), 7.33-7.40 (m, 1), 7.23-7.23 (m, 4H), 7.02-7.23 (m, 4H), 5.86 (q, J=6.6 Hz, 1H), 4.45 (s, 1H), 2.39-2.45 (m, 4H), 1.52-1.58 (m, 4H), 1.40-1.42 (m, 1H), 1.38 (d, J=6.6 Hz, 3H). LCMS: Anal. Calcd. for C21H24FNO2: 341. found: 342 (M+H)+.

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