반응 #1772025

반응 방정식

piperidine

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

DBU

CBr4

→

title compound

수율 11.1%

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

수율 11.1%

용매

diethyl ether toluene

THF

THF

반응 조건

후처리

1. 1
   온도The solution was then cooled to −78° C.
2. 2
   온도to warm to −10° C.
3. 3
   workup.STIRRINGstirred at this temperature for 2 hours
4. 4
   기타The reaction mixture was quenched with saturated aq. NH4Cl
5. 5
   기타the layers were separated
6. 6
   추출The aqueous layer was back-extracted with ethyl acetate (2×)
7. 7
   세척the combined organic phases were washed (H2O, brine)
8. 8
   건조dried (Na2SO4)
9. 9
   여과filtered
10. 10
    농축concentrated in vacuo
11. 11
    workup.STIRRINGthe solution was stirred at room temperature for 24 hours
12. 12
    농축The volatiles were then concentrated in vacuo
13. 13
    기타the residue was purified by silica gel chromatography (Biotage/0-30% diethyl ether-hexane)
14. 14
    기타to provide

실험 절차

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)+.

출처