تفاعل #46628

معادلة التفاعل

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

المردود 71.0%

المذيبات

THF

THF

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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)+.

المصدر