Reaction #46633

Reaction equation

product

(S)-tert-butyl 2-(2-(4-bromophenyl)-2-oxoethylcarbamoyl)pyrrolidine-1-carboxylate

PPh3

diisopropylethylamine

hexachloroethane

PPh3

hexachloroethane

→

(S)-tert-butyl 2-(5-(4-bromophenyl)oxazol-2-yl)pyrrolidine-1-carboxylate

Yield 63.3%

Solvents

CH3CN

—

hexanes

ethyl acetate

Conditions

Workup

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITcontinued for 4 hours
3. 3
   OtherThe solvent was removed in vacuo
4. 4
   workup.ADDITIONthe residue diluted with ethyl acetate-H2O
5. 5
   Otherthe layers separated
6. 6
   ExtractionThe aqueous phase was extracted twice with ethyl acetate
7. 7
   Washthe combined organic layers were washed (H2O, brine)
8. 8
   Dryingdried (Na2SO4)
9. 9
   Filtrationfiltered
10. 10
    OtherThe solvent was removed in vacuo
11. 11
    Otherthe residue purified by flash column chromatography (3:1 hexanes:ethyl acetate)

Procedure

To a solution of the product of Step 1 (1.00 g, 2.43 mmol), PPh3 (1.00 g, 3.71 mmol) and diisopropylethylamine (1.3 mL, 7.28 mmol) in CH3CN (30 mL) was added hexachloroethane (0.812 g, 3.43 mmol) as a solid, portion-wise. The mixture was allowed to stir for 12 hours. TLC (3:1 hexanes:ethyl acetate) indicated the presence of starting material. Therefore, additional PPh3 (0.65 g, 2.43 mmol) and hexachloroethane (0.575 g, 2.43 mmol) were added and stirring continued for 4 hours. The solvent was removed in vacuo, the residue diluted with ethyl acetate-H2O and the layers separated. The aqueous phase was extracted twice with ethyl acetate and the combined organic layers were washed (H2O, brine), dried (Na2SO4), and filtered. The solvent was removed in vacuo and the residue purified by flash column chromatography (3:1 hexanes:ethyl acetate) to provide (S)-tert-butyl 2-(5-(4-bromophenyl)oxazol-2-yl)pyrrolidine-1-carboxylate (0.605 g, 63%). 1HNMR (400 MHz, DMSO-d6) δ 7.60-7.68 (m, 5H), 4.80-4.91 (m, 1H), 3.46-3.51 (m, 1H), 3.33-3.39 (m, 1H), 2.18-2.31 (m, 1H), 1.84-1.99 (m, 3H), 1.36 (s, 4H), 1.15 (s, 5H). LCMS: Anal. Calcd. for C18H21BrN2O3: 392. found: 393 (M+H)+.

Source