Hydrochloric Acid → HCID 57692649, compound

HRID 2377597Notes

Reaction equation

HRID 2377597 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-b56953075ef848c4895c9a279022ffb4
Source dataset
uspto-grants-2008_12
Patent number
US07470664B2

Reaction notes

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