Methyl iodide → HCID 71270656, compound

HRID 2406261Notes

Reaction equation

HRID 2406261 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@@H:7]([N:11]1[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]1=[O:21])[C@@H:6]([OH:22])[CH2:5]2.O1CCC[CH2:24]1.CI.CC(C)([O-])C.[K+]>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@@H:7]([N:11]1[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]1=[O:21])[C@@H:6]([O:22][CH3:24])[CH2:5]2

Participants

5

Reactant 4

HCID 6328Methyl iodideHCID 8028Tetrahydrofuran2×HCID 23665647Potassium tert-butoxideHCID 71270645HCID 71270645, compound

Product 1

HCID 71270656HCID 71270656, compoundYield 96%

Conditions

Temperature
0 °C

Procedure

To a solution of 2-[(1R,2S)-5-chloro-2-hydroxy-2,3-dihydro-1H-inden-1-yl]-1H-isoindole-1,3(2H)-dione (25.8 g, 0.0822 mol) in tetrahydrofuran (186 mL, 2.29 mol) was added methyl iodide (20.5 mL, 0.329 mol) and the solution was stirred at 0° C. To this solution was added 1.00 M of potassium tert-butoxide in tetrahydrofuran (90.4 mL, 0.0904 mol) dropwise via an addition funnel over 1 hour. The reaction was quenched via addition of 0.1 N HCl (250 mL) and transferred to a separatory funnel containing EtOAc (600 mL). The layers were separated, and the organic layer was washed with 1N NaOH (2×100 mL each) and with brine (100 mL). The organic layer was dried over Na2SO4, filtered, and concentrated to afford 2-[(1R,2S)-5-chloro-2-methoxy-2,3-dihydro-1H-inden-1-yl]-1H-isoindole-1,3(2H)-dione (25.8 g, 96%) which was used without further purification in the next step.

Workup

  1. customThe reaction was quenched via addition of 0.1 N HCl (250 mL)
  2. customtransferred to a separatory funnel
  3. additioncontaining EtOAc (600 mL)
  4. customThe layers were separated
  5. washthe organic layer was washed with 1N NaOH (2×100 mL each) and with brine (100 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-ed50020d2fd548eb964be035b0c7cc7e
Source dataset
uspto-grants-2014_08
Patent number
US08809356B2

Reaction notes

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