Pyridine → HCID 86681698, compound

HRID 571293Notes

Reaction equation

HRID 571293 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C:5]2=[O:20].N1C=CC=CC=1.[CH3:27][S:28](Cl)(=[O:30])=[O:29]>C1COCC1>[CH3:27][S:28]([NH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([CH2:12][C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[C:5]2=[O:20])(=[O:30])=[O:29]

Participants

5

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 86681697HCID 86681697, compound

Product 1

HCID 86681698HCID 86681698, compoundYield 14.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 2-(5-amino-1,3-dioxoisoindolin-2-yl)acetate (14 g, 50.7 mmol) in THF (100 ml), pyridine (8.20 ml, 101 mmol) was added followed by methanesulfonyl chloride (7.74 ml, 101 mmol), and the resulting mixture was heated to reflux for 5 hours. The volatiles were removed under vacuum, the residue was dissolved in DCM (200 ml) and washed with 0.2M HCl (3×50 ml) and brine; the organic phase was dried over Na2SO4 and evaporated to dryness. The resulting solid was triturated with ethyl acetate, and the title compound was recovered by filtration (12.5 g). The mother liquors were evaporated in vacuo and purified by silica gel chromatography (DCM:AcOEt 10:1), affording additional 2.6 g of the title compound. These two batches were dissolved in DCM, combined, and the solvent was evaporated in vacuo to afford tert-butyl 2-(5-(methylsulfonamido)-1,3-dioxoisoindolin-2-yl)acetate (15.1 g, 42.6 mmol, 84% yield, MS/ESI+ 354.9 [MH]+).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux for 5 hours
  3. customThe volatiles were removed under vacuum
  4. dissolutionthe residue was dissolved in DCM (200 ml)
  5. washwashed with 0.2M HCl (3×50 ml) and brine
  6. dry with materialthe organic phase was dried over Na2SO4
  7. customevaporated to dryness
  8. customThe resulting solid was triturated with ethyl acetate
  9. filtrationthe title compound was recovered by filtration (12.5 g)
  10. customThe mother liquors were evaporated in vacuo
  11. custompurified by silica gel chromatography (DCM:AcOEt 10:1)

Sources & evidence

ORD record
ord-ddc5e71989dd4b0b840f1350561c2753
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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