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 2377600Notes

Reaction equation

HRID 2377600 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 (10.1 g, 41.4 mmol) in DMF (90 mL) under nitrogen was cooled to 0° C. Solid 1,1′-carbonyldiimidazole (6.70 g, 41.4 mmol) was added to the reaction. The contents of the reaction flask were warmed to room temperature and after 2 h a solution of 4-vinylisoindoline (6.00 g, 41.4 mmol) in DMF (10 mL) 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 ethyl acetate (4×250 mL). Combined organics were washed with brine, dried with anhydrous sodium sulfate, filtered and evaporated. Flash column chromatography eluting with hexane/ethyl acetate 70/30 gave the title compound as a white foam, 13.9 g (33.4 mmol, 81% yield). LRMS (ESI) m/z 417 [(M+H)+; calcd for C22H29N2O6: 417]

Workup

  1. additionwas added
  2. temperaturethen cooled
  3. extractionThe resulting mixture was extracted with ethyl acetate (4×250 mL)
  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/ethyl acetate 70/30

Sources & evidence

ORD record
ord-4e27d39d8dce44a8b02fb2438e4f3989
Source dataset
uspto-grants-2008_12
Patent number
US07470664B2

Reaction notes

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