Reaktion #46628

Reaktionsgleichung

N-(tert-butoxycarbonyl)-L-proline N′-methoxy-N′-methylamide

1-ethynyl-4-iodobenzene

ethylmagnesium bromide

→

(S)-tert-butyl 2-(3-(4-iodophenyl)propioloyl)pyrrolidine-1-carboxylate

Ausbeute 71.0%

Lösungsmittel

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeAfter 10 minutes the cooling bath was removed
2. 2
   TemperaturThe reaction mixture was then re-cooled to 0° C.
3. 3
   TemperaturThe reaction mixture was warmed to room temperature
4. 4
   workup.STIRRINGstirring
5. 5
   workup.WAITwas continued for 12 hours before the mixture
6. 6
   Sonstigewas quenched with saturated NH4Cl
7. 7
   workup.ADDITIONThe mixture was diluted with ethyl acetate/H2O
8. 8
   Sonstigethe layers separated
9. 9
   Extraktionthe aqueous phase was re-extracted with ethyl acetate (2×)
10. 10
    WaschenThe combined organic layers were washed (H2O, brine)
11. 11
    Trocknendried (Na2SO4)
12. 12
    Filtrationfiltered
13. 13
    Sonstigethe solvent was removed in vacuo
14. 14
    SonstigeThe resulting residue was purified by flash chromatography (hexane:ethyl acetate, 4:1)

Vorschrift

To a solution of 1-ethynyl-4-iodobenzene 6 (0.908 g, 3.98 mmol) in THF (20 mL) at −78° C. was added ethylmagnesium bromide (3M in ether, 1.39 mL, 4.18 mmol). After 10 minutes the cooling bath was removed and the solution was allowed to stir at room temperature for 1 hour. The reaction mixture was then re-cooled to 0° C. and added to a solution of N-(tert-butoxycarbonyl)-L-proline N′-methoxy-N′-methylamide 2 (0.970 g, 3.76 mmol) in THF (10 mL). The reaction mixture was warmed to room temperature and stirring was continued for 12 hours before the mixture was quenched with saturated NH4Cl. The mixture was diluted with ethyl acetate/H2O, the layers separated and the aqueous phase was re-extracted with ethyl acetate (2×). The combined organic layers were washed (H2O, brine), dried (Na2SO4), and filtered, and the solvent was removed in vacuo. The resulting residue was purified by flash chromatography (hexane:ethyl acetate, 4:1) to give (S)-tert-butyl 2-(3-(4-iodophenyl)propioloyl)pyrrolidine-1-carboxylate 7 (0.908 g, 71%) as a yellow oil which solidified on standing. 1H NMR (400 MHz, CDCl3) δ 7.72-7.76 (m, 2H), 7.26-7.30 (m, 2H), 4.49 (dd, J=8.8, 4.3 Hz, 0.3H), 4.29 (dd, J=8.5, 5.5 Hz, 0.7H), 3.59 (app t, J=6.7 Hz, 2H), 2.20-2.33 (m, 1H), 1.85-2.10 (m, 3H), 1.45, 1.40 (s, 9H, rotamers in 2:3 ratio). LCMS: Anal. Calcd. for C18H20INO3: 425. found: 326 (M+H-Boc)+.

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