Diethyl Malonate → Ethyl 3-aminobenzo[b]thiophene-2-carboxylate

HRID 634537Notes

Reaction equation

HRID 634537 reaction equation
C([O-])C.[Na+].C(OCC)(=O)[CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8].Cl[C:17]1[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[S:19][N:18]=1>CCO>[NH2:18][C:17]1[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[S:19][C:6]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8]

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 5981903-Chloro-1,2-benzisothiazoleHCID 2723922Sodium ethoxide

Product 1

HCID 731510Ethyl 3-aminobenzo[b]thiophene-2-carboxylateYield 76.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A dry 2-neck 500 mL round-bottom flask (RBF) was charged with sodium ethanolate (46.2 mL, 124 mmol), diluted with 151 mL absolute EtOH, cooled in an ice bath and treated dropwise with diethyl malonate (17.98 mL, 118 mmol) under an atmosphere of nitrogen. After stirring for 20 minutes, the ice bath was removed and 3-chlorobenzo[d]isothiazole (20.0 g, 118 mmol) was added in one portion and stirred for 24 hours. The reaction solution was quenched with water, extracted with ether and treated with excess 4 M HCl/dioxane. A pinkish-white precipitate was filtered off, suspended in water, basified with Na2CO3, extracted with ether, washed with water and brine, dried over sodium sulfate, filtered and concentrated to yellow solids (˜20 g) which were recrystallized from ethanol/water and dried in a vacuum oven at 60° C. for 3 hrs to give ethyl 3-aminobenzo[b]thiophene-2-carboxylate (19.9 g, 76% yield).

Workup

  1. temperaturecooled in an ice bath
  2. customthe ice bath was removed
  3. stirringstirred for 24 hours
  4. customThe reaction solution was quenched with water
  5. extractionextracted with ether
  6. additiontreated with excess 4 M HCl/dioxane
  7. filtrationA pinkish-white precipitate was filtered off
  8. extractionextracted with ether
  9. washwashed with water and brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated to yellow solids (˜20 g) which
  13. customwere recrystallized from ethanol/water
  14. customdried in a vacuum oven at 60° C. for 3 hrs

Sources & evidence

ORD record
ord-d15ef6f216d54888a47de35916f4b2c4
Source dataset
uspto-grants-2016_04
Patent number
US09324949B2

Reaction notes

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