Hydrochloric Acid → HCID 57692649, compound

HRID 1511538Notes

Reaction equation

HRID 1511538 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C@@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].[C:17]([N:24]1[CH:28]=[CH:27]N=[CH:25]1)(N1C=CN=C1)=[O:18].[Cl:29][C:30]1C=[CH:37][CH:36]=[C:35]2[C:31]=1CNC2.Cl.CN(C=[O:44])C>>[Cl:29][C:30]1[CH:31]=[CH:35][CH:36]=[C:37]2[C:27]=1[CH2:28][N:24]([C:17]([O:18][C@H:7]1[CH2:6][N:5]([C:9]([O:11][C:12]([CH3:13])([CH3:15])[CH3:14])=[O:10])[C@H:4]([C:3]([O:2][CH3:1])=[O:16])[CH2:8]1)=[O:44])[CH2:25]2

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 6228Dimethylformamide2×HCID 682631,1'-CarbonyldiimidazoleHCID 1277666Boc-L-Pro-OmeHCID 147958684-Chloro-2,3-dihydro-1H-isoindole

Product 1

HCID 57692649HCID 57692649, compoundYield 66%

Procedure

To a solution of N-Boc proline methyl ester (2.87 g, 11.7 mmol) in DMF (15 mL) at 0° C. was added carbonyldiimidazole (1.9 g, 11.7 mmol). The reaction was warmed to room temperature and stirred for 30 min. A solution of 4-chloroisoindoline (1.8 g, 11.7 mmol) in DMF (10 mL) was then added and the reaction mixture was heated to 50° C. and stirred for 2 h. The reaction mixture was poured onto ethyl ether and 0.5 M HCl and the layers were separated. The organic layer was washed with water, dried over Na2SO4, filtered and concentrated. The crude product was purified on silica gel (gradient elution 10% to 90% ethyl acetate in hexanes) to give 1-tert-butyl 2-methyl (2S,4R)-4-{[(4-chloro-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}pyrrolidine-1,2-dicarboxylate (3.3 g, 66% yield). LRMS (ESI) m/z 325 [(M+H-Boc)+; calcd for C15H18ClN2O4: 325].

Workup

  1. temperaturethe reaction mixture was heated to 50° C.
  2. stirringstirred for 2 h
  3. customthe layers were separated
  4. washThe organic layer was washed with water
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified on silica gel (gradient elution 10% to 90% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-da42cc5c0e0c4c7dbd50460057024260
Source dataset
uspto-grants-2012_07
Patent number
US08216999B2

Reaction notes

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