1,1'-Carbonyldiimidazole → 1-t-Butyl 2-methyl (2S,4R)-4-{[(4-vinyl-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}pyrrolidine-1,2-dicarboxylate

HRID 1879250Notes

Reaction equation

HRID 1879250 reaction equation
[OH:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1.[C:18]([N:25]1[CH:29]=[CH:28]N=[CH:26]1)(N1C=CN=C1)=[O:19].[CH:30]([C:32]1C=[CH:39][CH:38]=[C:37]2[C:33]=1CNC2)=[CH2:31].S(=O)(=O)(O)[O-].[K+]>CN(C=O)C.O>[CH:38]([C:37]1[CH:33]=[CH:32][CH:30]=[C:31]2[C:28]=1[CH2:29][N:25]([C:18]([O:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1)=[O:19])[CH2:26]2)=[CH2:39]

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 516920Potassium bisulfateHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterHCID 534871884-Ethenyl-2,3-dihydro-1H-isoindole

Product 1

HCID 453783721-t-Butyl 2-methyl (2S,4R)-4-{[(4-vinyl-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}pyrrolidine-1,2-dicarboxylateYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of 1-tert-butyl 2-methyl (2S,4R)-4-hydroxypyrrolidine-1,2-dicarboxylate (1.0 eq.) in DMF (0.5 M) under nitrogen was cooled to 0° C. Solid 1,1′-carbonyldiimidazole (1.0 eq.) was added to the reaction. The contents of the reaction flask were warmed to RT and after 2 h a solution of 4-vinylisoindoline (1.0 eq.) in DMF (4 M) was added. The reaction was heated in a 60° C. oil bath for 2 h then cooled and poured into water and 5% potassium bisulfate. The resulting mixture was extracted with EtOAc. Combined organics were washed with brine, dried with anhydrous sodium sulfate, filtered and evaporated. Flash column chromatography eluting with hexane/EtOAc 70/30 gave the title compound as a white foam (81%). LRMS (ESI) m/z 417 (M+H).

Workup

  1. additionwas added
  2. temperaturethen cooled
  3. extractionThe resulting mixture was extracted with EtOAc
  4. washCombined organics were washed with brine
  5. dry with materialdried with anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. washFlash column chromatography eluting with hexane/EtOAc 70/30

Sources & evidence

ORD record
ord-00eb0678e2114a8298114d8ba159ba53
Source dataset
uspto-grants-2012_11
Patent number
US08314062B2

Reaction notes

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